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DAO Enzyme and Migraine: Unraveling the Histamine Connection

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Exploring the Role of Diamine Oxidase in Migraine Management and Prevention

Are you ready to dive into this topic of histamine intolerance, migraines, and the DAO enzyme together? Wondering if there might be an easy solution hiding in plain sight for your painful headaches? 

In this article, we’ll introduce you to a fascinating connection that could help unravel the mystery of your migraines once and for all. 

The DAO enzyme, or diamine oxidase, is essential for breaking down histamine in your body. Histamine is a signaling molecule involved in inflammation that can trigger migraine pain. 

When DAO levels are too low, excess histamine circulates in the bloodstream, resulting in histamine intolerance – negative reactions to foods high in histamine like aged cheese, pickled foods, and processed meats. Here’s where migraines come in.

In many migraine sufferers, histamine intolerance developed from impaired DAO, creating an imbalance of histamine that leads to inflammation, vasodilation, and the symptomatology of migraines. 

By boosting DAO levels, you may find significant relief from painful migraine attacks. Do certain diets, supplements, or other nutritional strategies work for controlling your migraines? 

Let’s explore how increasing DAO and mitigating histamine overload could provide a solution. 

Understanding Histamine and Its Role in Migraines

Histamine is an important signaling molecule in your body that helps regulate immunity, digestion, circulation, sleep, and mood. In small doses, histamine acts as a neurotransmitter and hormone. However, too much histamine circulating in the blood can become problematic. 

Excess histamine acts as a trigger for migraines by causing inflammation in blood vessels and tissues of the brain. This leads to swelling, pain, and changes in blood flow that result in the symptoms of migraine pain, nausea, sensitivity to light and sound, and blurred vision. 

When high levels of histamine dilate and constrict blood vessels rapidly, it creates an unstable environment that manifests as migraine pain. 

Histamine promotes inflammation by activating inflammatory pathways and leukocytes. This chronic, low-level inflammation creates perfect conditions for migraines to develop and persists between attacks further sensitizing the nervous system. 

Some of the most common sources of excess histamine include: 

  • Aged foods like cheese, wine, cured meats (salami, bacon, etc.) 
  • Fermented foods (sauerkraut, kimchi, miso, tempeh, natto, etc.) 
  • Food additives such as monosodium glutamate (MSG) 
  • Medications including some pain relievers, decongestants, and allergy medicines 
  • Stress, lack of sleep, hormonal changes, and sensory sensitivities 

The Crucial Role of DAO Enzyme in Histamine Homeostasis

The DAO enzyme, or diamine oxidase, is vital for maintaining healthy histamine levels in your body. DAO helps break down excess dietary histamine from foods and also metabolizes any histamine produced or released internally. 

When DAO activity is low, it results in impaired histamine breakdown and imbalanced, elevated histamine that contributes to conditions like histamine intolerance and migraines. 

DAO requires certain cofactors like vitamin B6, riboflavin, folate, and vitamin C to function properly. Issues with any of these can negatively impact your DAO levels and histamine metabolism. Medications, age, smoking, and heavy alcohol use may also decrease DAO activity, allowing excess histamine to build up. 

Chronic inflammation and leaky gut syndrome further diminish DAO, creating a vicious cycle of histamine overload, gut permeability issues, and inflammation that manifests as migraines, digestive problems, skin conditions, and other symptoms. 

The link between inadequate DAO, excess histamine, and migraine occurrence is profound. Several studies have found significantly lower DAO enzyme activity and higher urinary histamine levels in migraine patients compared to non-migraine controls. 

By supplementing with a high-quality DAO enzyme and cofactors, reducing inflammation, and avoiding exacerbating factors, DAO activity and histamine homeostasis can be restored. 

In summary, maintaining healthy DAO levels through diet, supplements, self-care, and managing any underlying conditions is crucial for controlling histamine and preventing migraines. 

Symptoms and Conditions Related to Histamine Intolerance

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Many people with histamine intolerance experience a slew of troublesome and unexplained symptoms, often confusing them or making their condition difficult to diagnose. Headaches, including migraines, are among the most common symptoms associated with excess histamine. Other signs include:

Allergic reactions: Hives, itching, swelling of the lips, tongue, throat, etc. 

Gastrointestinal issues: Bloating, diarrhea, abdominal pain, IBS, ulcerative colitis, Crohn’s disease. 

Fatigue and lack of focus: Histamine inhibits the production of serotonin, a mood-regulating neurotransmitter. 

Sensitivity to light, sound, and other sensory input. 

Skin inflammation: Eczema, psoriasis, dermatitis. 

Anxiety and mood changes: Anxiety, depression, irritability, insomnia. 

These symptoms are often misdiagnosed or perceived as unrelated issues when in reality, they originate from a systemic histamine overload. Identification of food triggers and an elimination diet focusing on high-histamine foods are pivotal for managing symptoms and re-establishing proper histamine levels. 

Food triggers of histamine intolerance include: 

Food Triggers of Histamine IntoleranceExamples
Fermented foodsSauerkraut, kimchi, natto, miso, tempeh
Preserved foodsPickles, sausages, bacon, ham, salami, anchovies
DairyAged cheese, yogurt, kefir, butter
AlcoholWine, beer, liquor
AdditivesMSG, tyramine

By avoiding triggers, supplementing for any deficiencies, supporting a healthy gut, reducing overall inflammation and optimizing DAO activity, you can alleviate symptoms and start to feel normal again. 

Low-Histamine Diet for Migraine Management

Following a low-histamine diet can be extremely helpful for controlling migraines, especially if excess histamine is contributing to your symptoms. By reducing histamine intake from foods and supplements, you help ensure proper balance and breakdown of any histamine in the body. 

This anti-inflammatory diet focuses on foods that are naturally low in histamines while avoiding common histamine triggers like aged cheeses, fermented foods, preserved meats, and alcohol. 

Some key benefits of a low-histamine diet for migraines include:

Decreased inflammation. A low-histamine diet reduces excess histamine that can drive chronic inflammation and promote migraine pain. 

Improved DAO activity. When histamine levels remain stable and balanced, your body can better regulate DAO production and break down any histamine effectively. This helps maintain homeostasis. 

Symptom relief. By eliminating histamine triggers from your diet, especially at first, you cut off the fuel source for your migraine symptoms like pain, nausea, light/sound sensitivity, etc. Symptoms will improve substantially over time. 

Frequency reduction. As histamine balance is achieved and optimized, migraines may decrease in frequency and intensity. For some, nearly eliminating migraines altogether is possible. 

Gut healing. A low-histamine, anti-inflammatory diet also supports gut health and permeability. This helps address any underlying roots of excess histamine production in the leaky gut. 

Be sure to avoid common high-histamine foods like: 

Fermented foods: Sauerkraut, kimchi, miso, tempeh, natto, kefir, yogurt, etc. 

Preserved meats: Salami, pepperoni, bacon, ham, prosciutto, etc. 

Aged cheese: Parmesan, cheddar, gouda, manchego, etc. 

Alcohol: Wine, liquor, beer, cider, etc. 

Instead, focus on low-histamine, whole foods such as:

Low-Histamine Whole FoodsExamples
MeatFresh chicken, fish, and grass-fed beef
VegetablesLeafy greens, broccoli, cucumbers, peppers, zucchini, etc.
FruitBerries, citrus, melon, papaya, etc.
GrainsBuckwheat, millet, oats, brown rice, quinoa
LegumesLentils, beans, peas
Nuts and seedsAlmonds, pumpkin seeds, sunflower seeds
OilsCoconut, olive, avocado
Herbs and spicesFresh and dried herbs and spices

DAO Supplements and Migraine Prevention

Supplementing with DAO, or diamine oxidase, can be an effective preventive strategy for migraines, especially when excess histamine contributes to your symptoms. 

Several studies have found that migraine patients tend to have significantly lower serum DAO levels and diamine oxidase activities compared to non-migraine controls. 

By providing the DAO enzyme in supplemental form, histamine breakdown can be optimized and balanced, decreasing the likelihood of migraine pain.

Some key benefits of DAO supplements for migraine prevention include:

Increased histamine metabolism. DAO supplements directly provide the enzyme needed to properly break down excess histamine from foods, inflammation, and other sources. This helps maintain healthy histamine levels. 

Reduced inflammation. When histamine is kept in check, chronic inflammation is decreased. This anti-inflammatory effect can help prevent migraine triggers from activating. 

Stabilized symptoms. Supplementing with DAO may provide stability and relief from bothersome symptoms like gastrointestinal issues, skin irritation, anxiety, and sensitivity to lights/sounds which could otherwise promote migraine pain. 

Decreased migraine frequency. For those with frequent migraines, DAO supplements have the potential to significantly cut down on the number of headache episodes over time by addressing an underlying mechanism of excess histamine. 

Pre-emptive treatment. Taking a DAO supplement, especially with a high-histamine meal or in anticipation of encountering migraine triggers, acts as a preventive treatment to avoid symptom flare-ups altogether. 

Points to keep in mind with DAO supplements:
Choose a high-quality, enteric-coated supplement to ensure proper absorption.
The typical dosage for migraine prevention is 100-300 mg, 2-3 times per day.
It can take several weeks of use to notice the full benefits on symptoms and migraine frequency. Be patient and consistent.
You may need to experiment with different doses to find what works best for you. Monitor how you feel at each dose.
DAO supplements are generally well tolerated, but possible side effects may include diarrhea, abdominal pain, and rash. Discontinue use if intolerable side effects develop.
DAO supplements may interact with some medications. Check with your doctor or pharmacist first, especially if you take blood thinners or high blood pressure medications.

Supplementing with DAO offers promising potential as a preventive strategy for migraines when excess histamine underlies your symptoms. By optimizing histamine breakdown, DAO supplements help reduce inflammation, stabilize balance, and decrease migraine frequency and pain over time. 

Strategies To Help Manage Histamine-related Migraines

Support gut health

Your gut plays a crucial role in regulating histamine levels and metabolism. A healthy digestive system is needed to properly break down histamine from foods and any excess production. 

Some tips for gut health include: 

  • Eat probiotic foods or supplements to promote good bacteria. 
  • Limit antibiotics which kill beneficial bacteria. Only use when medically necessary. 
  • Avoid inflammatory foods that can damage the gut lining like gluten, refined grains, and sugar. 
  • Manage any underlying conditions like SIBO, Candida overgrowth or leaky gut. Treatments include probiotics, digestive enzymes, and antimicrobial herbs.

Reduce histamine triggers

Minimize exposure to triggers that increase histamine release and activity. This includes:

  • Alcohol: All types of alcohol trigger histamine release. Avoidance is ideal for management. 
  • Stress: Managing stress levels with relaxation techniques like yoga or meditation helps keep histamine in check. 
  • Fluctuations in hormone levels: For those with monthly menstrual cycles or perimenopause/menopause, histamine levels can shift dramatically with hormone changes. Hormonal birth control may help provide more stability.

Seek medical guidance

If lifestyle changes are not enough to gain control of your histamine-related migraines, consult with your doctor. Other treatment options may be helpful such as:

  • Medications: Certain antidepressants, antihistamines, and corticosteroids can help reduce excess histamine activity. 
  • Botox injections: Botox is sometimes used to prevent migraine pain by relaxing tense blood vessels and muscles. 
  • IV treatments: IV glutathione, vitamin C, magnesium and hydration help support detoxification and histamine breakdown. 
  • Other procedures: Occipital nerve stimulation, transcranial magnetic stimulation, occipital cortical stimulation provide pain relief through stimulation of the nerves and cortex involved in migraine pain.

The key is finding an integrated approach tailored to your own symptoms and needs. Lifestyle strategies should form the foundation, with medical treatments reserved for severe or intractable cases. 


In conclusion, excess histamine and impaired DAO enzyme activity have potential links to migraine pain and frequency. By supplementing with DAO, following a low-histamine diet, reducing histamine triggers, and maintaining gut health, histamine balance can be optimized, decreasing inflammation and preventing migraines. 

Key Takeaways:

Histamine overload may drive chronic inflammation and promote migraine pain. Balanced histamine levels help prevent inflammation flares. 

DAO supplements provide the enzyme needed to properly break down excess histamine, supporting homeostasis. Adequate DAO activity is essential for managing histamine intolerance

A low-histamine diet eliminates excess histamine from foods and ensures you get all the nutrition you need without trigger effects. This helps stabilize symptoms and decrease migraines over time. 

Gut health impacts how well your body regulates histamine and other biogenic amines. A healthy gut flora improves histamine metabolism and barrier integrity, reducing symptom severity. 

Considering additional contributing factors like hormones, inflammatory foods, medication use and other triggers also helps gain more comprehensive control over migraines. An integrated approach works best. 

Schedule a Free Consultation With SeeBeyond Medicine

For those continuing to struggle with frequent or intense migraine pain, exploring the possible role of excess histamine and impaired DAO enzyme activity further with your doctor is warranted. Diagnosing and addressing any underlying imbalances in histamine regulation may improve your migraine prevention and treatment.

Don’t lose hope if migraines are impacting your life. By developing a deeper understanding of the mechanisms involved and taking a multi-disciplinary approach to management, your ability to gain control over excess histamine and prevent migraines expands considerably. 

With patience, persistence and personalized guidance, many are able to eliminate migraines altogether or at least develop a comprehensive treatment plan for optimized health and well-being. 

We are offering 30 minutes for free to talk to one of SeeBeyond's Functional Medicine Practitioners to create a personalized regimen.

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