Understand Diamine Oxidase & Manage Your Histamine in 5 Steps

• What Is Histamine Intolerance?|
• Causes of Low DAO|
• Pros & Cons of DAO Supplements|
• 5-Step Histamine Intolerance Plan|

If you’ve reacted poorly to perfectly normal foods—maybe you’ve gotten a headache, an upset stomach, or even a rash after eating certain meals—you might be dealing with symptoms of histamine intolerance. 

Histamine intolerance, also known as histamine sensitivity, is surprisingly common and often linked to the digestive enzyme diamine oxidase (DAO). This enzyme helps break down histamine, an essential compound for immune responses and digestion.

When DAO is unable to do its job properly, histamine can build up, leading to symptoms like gas, bloating, food allergy, skin issues, and even migraines. 

In this article, we’ll dive into how diamine oxidase works and the potential benefits (and downsides) of DAO supplements. We’ll also explore other natural ways to support levels of DAO and relieve histamine intolerance symptoms.

First, let’s look more closely at histamine metabolism, what histamine intolerance is, and the symptoms it causes.

What Is Histamine Intolerance?

Histamine intolerance occurs when the body cannot fully break down and get rid of histamine, a natural compound (biogenic amine) that plays a vital role in various bodily functions. 

Certain immune system cells make most of the body’s histamine, which helps us digest food, grow blood cells, and have a functional central nervous system. However, histamine is best recognized for its role in allergic reactions because it causes itchiness, swelling, and redness as part of the inflammatory response.

The normal bacteria in some foods and drinks can also produce histamine, which enters the body when we eat and drink.

When the body breaks down and gets rid of excess histamine efficiently, all is well. But if you don’t degrade histamine properly and the chemical accumulates, it can lead to symptoms.

Limited data makes it hard to determine the prevalence of histamine intolerance. However, estimates suggest it affects 1–3% of people in the USA, a statistic that may increase as awareness and diagnostic tools improve 1. 

As I shared in this recent histamine intolerance podcast, histamine intolerance could play a part in 30–55% of people with nonspecific gastrointestinal symptoms, like abdominal pain 2.

When people are sensitive to high concentrations of histamine, their symptoms can range widely, as shown below 3 4 5:

What Causes a Low DAO Level?

It’s not clear exactly what leads to DAO deficiency or low DAO enzyme activity, but our genetic makeup and age (being over 40) might contribute 6. 

Gut inflammation and related dysbiosis—disruptions in the balance of healthy gut bacteria—are also potential contributors 7. Many of my clients who improve their gut health notice significant improvements in their histamine intolerance symptoms. We’ll explore this in more detail below.

Certain medications can reduce DAO levels or its effectiveness. These include 8:

• NSAIDs like aspirin or ibuprofen
• Prokinetics like metoclopramide
• Antibiotics like doxycycline or neomycin B
• Antidepressants such as MAO inhibitors or amitriptyline
• Anxiety medications like diazepam or barbiturates
• Opioids such as morphine or codeine

Hormonal fluctuations during the menstrual cycle are another possible factor in low DAO levels. For instance, when estrogen drops at the start of a period, DAO levels can decrease, which may contribute to worse cramping during menstruation 9.

Can You Test for Low Diamine Oxidase Levels?

There are actually two enzymes that break down histamine—diamine oxidase (DAO) and histamine-N-methyltransferase (HNMT).

The reason we’re most focused on DAO is because this enzyme resides largely in the small intestine and is especially important for breaking down histamine that comes from food 10.

Test kits that check for serum diamine oxidase activity are available online. We don’t routinely recommend them to clients, but if you buy a diamine oxidase test kit, you’ll typically just need to perform a simple finger prick to provide a small blood sample.

Opinions vary on the interpretation of DAO levels, but a common guideline suggests that levels below 10 U/ml may indicate an increased risk of histamine intolerance 2.

A DAO test, or assay, is just a small piece of the puzzle when treating histamine intolerance. We can usually get farther and spend less time and money by evaluating a client’s symptoms and whether they feel better while trying a low histamine diet.

The Pros and Cons of Diamine Oxidase Supplementation

Given DAO’s role in histamine intolerance, supplementing with the enzyme might seem like an obvious choice for managing high-histamine symptoms. 

However, the research on DAO is still limited. Here’s what we currently know about its potential benefits and drawbacks.

Benefits of DAO Supplements 

Randomized controlled trials (RCTs), considered the gold standard of human research, have suggested that DAO supplements may help people with conditions potentially linked to too much histamine.

The findings are summarized in this table:

Downsides of DAO Supplements

Although DAO supplements appear to be safe, we only have a few well-designed human studies from which to draw this conclusion 8. 

In general, there’s not enough evidence to know:

• If DAO can clearly help with histamine intolerance
• How much DAO is ideal to take
• Whether DAO may cause negative side effects during long-term use

Something else to bear in mind is that most (if not all) diamine oxidase supplements are made from pig kidneys 8. This could be a problem if your religion or diet restricts pork or animal products.

Although we sometimes use DAO and other histamine-reducing supplements in the clinic, we usually save them for later in a client’s treatment program. DAO supplements are not our first-line approach because there are more effective and fundamental strategies for addressing histamine intolerance and its underlying causes.

A 5-Step Plan for Treating Histamine Intolerance

DAO supplements alone can be very helpful for some people with histamine intolerance. But typically in the clinic, we find a more root-cause approach is essential for managing the condition. For long-term relief, we focus on addressing the underlying causes with the following 5 steps.

Step 1: Implement a Low Histamine Diet and Address Gut Health

When we suspect histamine intolerance, the best way to reach a diagnosis is usually to have clients try a low histamine diet. For a period of time, they avoid these four main categories of histamine-rich food:

• Any aged food, such as mature cheese or aged meat, or leftovers
• Any fermented food or drink, such as sauerkraut or red wine
• Various types of cured and canned meat or fish
• Shellfish

Compared with many strict elimination diets, a low histamine diet isn’t too difficult to do. The table below shows how we advise clients to make wholesome switches that reduce histamine while ensuring happy tastebuds and enough nutrients.

In case this looks different from other high/low histamine lists you’ve seen, know that not every food listed in the “avoid” column is a histamine-rich food. Some foods listed may stimulate histamine production or inhibit DAO activity, leading to a similar outcome: an increased likelihood of histamine intolerance symptoms. 

Regardless, these dietary swaps are the ones I’ve found to be most effective in my clinical practice.

When following a low histamine diet, it’s important not to stress over the occasional high-histamine meal—planned or accidental. For most people, an 80:20 approach (staying on target 80% of the time) is enough to manage symptoms effectively.

Histamine-intolerant folks usually notice their symptoms improve within 1–2 weeks of starting a low histamine diet. If not, and depending on their symptoms, we may move into trialing a low FODMAP diet or a Candida diet.

Take Care of Your Gut Microbiota

Alongside a low histamine diet it’s also helpful to support the health of the gut microbiota by taking probiotics. Though research is in its early stages, it’s thought that dysbiosis, or a disrupted balance of healthy bacteria in the gut, may play a role in histamine intolerance 15. 

For example, people with histamine intolerance may have reduced microbiota diversity and lower Bifidobacterium counts 16. They may also have higher levels of bacteria that secrete histamine 17. Such changes in healthy gut bacteria may contribute to inflammation of the gut lining (intestinal mucosa) and less effective DAO. 

In the clinic, we’ve found that the most effective probiotic is one that combines different species, such as a blend of Lactobacillus and Bifidobacterium species, a beneficial yeast, and a soil-based probiotic.

Some out-of-date claims still lurking on the internet suggest that probiotics produce histamine and should be avoided in histamine intolerance. However, the only study we’ve found on probiotic histamine production showed that a multistrain probiotic made very little histamine in a petri dish 18. 

What’s more compelling, though, is a meta-analysis (highest quality study of studies) that found that multi-strain probiotics can improve allergy symptoms related largely to histamine 19.

In addition to probiotics, a few other gut supports we’ve found clinically useful for patients with stubborn histamine-like symptoms include: 

• An elemental diet (specifically a 2–4 day gut reset)
• Herbal antimicrobials, such as oregano oil, garlic, and wormwood
• L-glutamine at 10–15 g/day

Step 2: Stabilize Mast Cells with Supplements

Mast cells play a key role in histamine intolerance. Found especially in the skin, lungs, and digestive tract, they are immune cells that store and release histamine when they come into contact with certain stimuli. 

Common triggers of histamine release by mast cells include allergens, infectious organisms like bacteria or viruses, physical stimuli like heat or friction, certain foods, and stress. 

Overactive mast cells can contribute to excess histamine, which worsens symptoms. But it’s possible to stabilize mast cells, reducing their histamine release and the inflammation that follows.

More research is needed, but lab studies and human trials have found that the following may be effective mast cell stabilizers 20:

• Quercetin 
• Resveratrol 
• Curcumin
• Vitamin D
• Benifuuki green tea (EGCG)

I’d also add luteolin and melatonin to this list given that: 

• The anti-inflammatory compound luteolin outperformed cromolyn (a mast cell stabilizing medication) at reducing histamine release and inflammatory cytokines in a petri dish study 21. 
• The sleep hormone melatonin showed potential for reducing mast cell activity by blocking inflammatory pathways in a petri dish 22.

We’re waiting for more research to confirm which of these supplements can actually relieve histamine intolerance in people. But they’re generally safe to try, and we’ve had good clinical results using one or more of them, as outlined in the following protocol.

The doses are based on what studies have used successfully and what our histamine-intolerant clients report as helpful.

Step 3: Boost the Body’s Ability to Metabolize Histamine

Having an optimal intake of vitamins and minerals is important for metabolizing histamine. The following micronutrients may help DAO break down histamine:

• Vitamin C (in a study, 2,000 mg/day decreased blood serum histamine by 38%) 23
• Vitamin B6 (especially the pyridoxal-5-phosphate form) 8
• Copper 8
• Zinc 8

Although a healthy, balanced diet should supply these nutrients, supplements can help you achieve the higher intakes we find useful for histamine intolerance.

When we use supplements to support a faster, more efficient breakdown of histamine, these are the micronutrients and doses we use:

If you want to add these supplements to your own regime, taking them with or after a meal is usually the best. However, you should check with your own healthcare provider about which products and doses are right for you.

Step 4: Directly Break Down or Block Histamine

If my clients are still troubled by high-histamine symptoms after implementing steps 1–3, we will try a DAO supplement. At this point, it becomes clear when someone needs direct enzymatic help to break down histamine.

When diamine oxidase is called for, we have clients take at least 10,000 HDU (histamine degrading units) before meals 8.

For those who are open to conventional medications, antihistamines are also an option. Usually available over the counter, these drugs block histamine receptors and can be good for short-term support, taken as needed.

The two types of antihistamines are:

• H1 blockers: Zyrtec, Claritin
• H2 blockers: Pepcid, Zantac

You should check with your own doctor about proper dosing, but our clients who need them usually take both an H1 blocker and an H2 blocker each day.

Step 5: Address Other Culprits

If other factors could be contributing to your histamine intolerance symptoms, it’s important to address them.

For example, female hormonal imbalances, stress, environmental toxins, and infections may all play a part.

Female Hormone Imbalances

I already alluded to the fact that the menstrual cycle can affect diamine oxidase, with levels declining alongside estrogen and progesterone hormones before menstruation 9. 

To support a healthy hormone balance in women who get histamine symptom flares (manifesting mainly as menstrual cramps), we often recommend using the following herbs, or a curated combination of them:

• Black cohosh
• Dong quai
• Licorice root extract
• Chaste berry extract
• DIM (Diindolylmethane)

It’s best to check with your practitioner to figure out which hormone balancing herbs might be best for your own symptoms of histamine intolerance.

Unmanaged Stress

Stress may also play a role in histamine intolerance. For example, in lab studies, stress hormones like CRH (corticotropin-releasing hormone) can activate mast cells 24. 

Science-based ways to manage stress include:

• Yoga
• Meditation
• Cognitive behavioral therapy (CBT)
• Time in nature (if allergies aren’t a concern)
• Limbic system retraining, like The Gupta Program

Environmental Exposures

Mold, chemicals, and allergens can trigger mast cells to release histamine 25. To manage this, it’s important to identify and reduce exposure to these toxic triggers whenever possible.

Infectious Organisms

Infectious organisms can also stimulate mast cells and contribute to histamine-like symptoms 26. Examples include:

• Vector-borne microbes like Borrelia, Babesia, and Bartonella
• Viruses
• Parasites
• H. pylori
• Candida
• Small Intestinal Bacterial Overgrowth (SIBO)

Addressing any infections that might be triggering mast cell activity is an important step toward managing symptoms of histamine intolerance.

Diamine Oxidase Isn’t the Only Factor in Histamine Intolerance

Diamine oxidase (DAO) plays a key role in breaking down histamine, but it’s only one piece of the puzzle. Factors like gut health, mast cell activity, stress, hormonal imbalances, and environmental triggers may all contribute to histamine intolerance and its symptoms.

By adopting a holistic approach—including dietary adjustments, gut support, targeted supplements, and lifestyle changes—you can reduce your histamine load at the root and regain control over your symptoms. DAO supplements and antihistamines can provide additional relief, but they’re most effective when used in combination with strategies that address root causes.

If you need help walking through the 5-step process outlined in this article, you can subscribe to and download our Histamine Intolerance Handout. Alternatively, you can get in touch with one of our practitioners at the Ruscio Institute for Functional Medicine.

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