Histamine And Migraine: Is There A Connection? 

If you live with migraine disease, you likely know that there are some guidelines you need to try and follow: avoid your triggers, stay hydrated, have good sleep hygiene, and much more! Yet, for many, the “thunderstorm” in the brain frequently arrives anyway, despite your best efforts. If your migraine triggers seem random, come after a meal, or are accompanied by things like flushing, itching, or digestive upset, it might be to do with something called your mast cells.

To understand why, we have to look at histamine; a powerful chemical found in those mast cells which typically are associated with allergies. 

Histamine and the Migraine Connection

Most people know histamine as a “chemical” that causes allergy symptoms during hayfever season. However, in reality, histamine performs many functions. It regulates stomach acid, acts as a neurotransmitter in the brain, and (most importantly for people with migraine) it is a potent vasodilator, meaning that it dilates (swells, expands) blood vessels. 

When histamine levels spike, blood vessels dilate. In the brain, this process can irritate the trigeminal nerve, the main sensory nerve of the head and face, and a pathway involved in migraine. This irritation can lead to neurogenic swelling, which then triggers migraine attacks.

In addition, allergies also cause inflammation in general, which in turn can increase the frequency of migraine attacks. The relationship between migraine and narrowing of the airways suggests that inflammation is an underlying mechanism in migraine. We also know that asthma and migraine are linked by parasympathetic hyperactivity, which is why an irritant like perfume can trigger both asthma and migraine attacks. (¹)  

Mast Cells: The Body’s Security Guards

Histamine is stored in mast cells, often called the “security guards” of your immune system. These cells are in tissues that interface with the outside world, including the protective layers of your brain. 

In some people, these cells become overactive, a condition known as Mast Cell Activation Syndrome (MCAS). In MCAS, mast cells burst (degranulate) and release a flood of histamine and inflammatory chemicals such as histamine, serotonin, and cytokines in response to minor stressors such as heat, scent, or even emotional stress. If you find that your migraine attacks are triggered by almost anything, it is possible that your mast cells may be to blame!

According to the National Institutes of Health, MCAS is considered a rare disease, and its cause is unknown. It is diagnosed based on symptom history and diagnostic blood and urine tests. However, it is likely that it is greatly under-diagnosed! 

The “Bucket” Theory of Histamine Intolerance

Think of your body’s ability to handle histamine like a bucket. You can tolerate a certain amount, but once the bucket overflows, a migraine begins. Your bucket fills up through things such as:

• Diet: high-histamine foods like fermented vegetables, aged cheeses, cured meats, and alcohol
• Environment: pollen, mold, and chemicals
• Internal Production: stress and immune responses

Normally, an enzyme called Diamine Oxidase (DAO) acts like a drain at the bottom of the bucket, breaking histamine down. However, many migraine patients have Histamine Intolerance (HIT), meaning that their “drain” is clogged. Whether due to genetics or poor gut health, they can’t clear histamine fast enough, leading to a toxic buildup that results in a migraine attack.

Recognizing the Signs of Histamine Intolerance 

So how do you know if histamine is triggering your migraine attacks? Look for symptoms that are usually considered allergy-like, which occur together with or just before your attack. Symptoms can be any of the following:

• Skin: flushing of the neck/face, hives, or itching
• Digestion: bloating or diarrhea immediately after eating
• Respiratory: a runny or stuffy nose during an attack
• Cardiac: racing heart or palpitations

Does a Low Histamine Diet Help?

For some people, dietary histamine may play a role in migraine symptoms. Some foods and alcoholic beverages that are high in histamine could trigger or worsen migraine attacks, and symptoms may be worse in individuals with histamine intolerance. Some foods that have higher levels of histamine include:

• Fermented foods:  yogurt, sour cream, cheese, tempeh, miso, sauerkraut, sausage, and grains such as sourdough bread
• Fruits and vegetables:  tomatoes, eggplant, spinach
• Fish (frozen, salted, canned):  tuna, sardines
• Alcohol:  wine, beer, champagne
• Misc:  kombucha, pickles, vinegar, tomato ketchup

Low-histamine diets can be very restrictive and hard to follow, and may lead to poor nutrition. However, when used short-term, it may help diagnose histamine intolerance. Talk with your doctor or a registered dietician about this before making major changes to your diet. 

How to Take Control of Histamine and Migraine

If this sounds like what is happening to you, there is hope! Managing histamine is often about lowering the total load on your system rather than finding a single “cure.”

1. Seek an official diagnosis:  your medical team, including your primary care doctor and headache specialist, can help make a diagnosis. This includes a symptom history, physical exam, and specific lab tests. 
2. The Low-Histamine Trial: under the supervision of your doctor, focus on foods that are low in histamine and monitor any improvement.
3. Support the “Drain”: some patients find relief by taking DAO supplements before meals to help break down dietary histamine. Talk with your doctor about which supplements may work best for you. 
4. Stabilize the Cells: natural mast cell stabilizers, such as Quercetin, or pharmaceutical antihistamines (under a doctor’s care) can help keep your “security guards” from overreacting.
5. Follow your Migraine Action Plan: develop a treatment plan with your doctor that includes managing triggers like histamine.

Migraine is a complex neurological disease, but for many, it is also an immunological one. By understanding the role of histamine and mast cells, you may be able to move beyond simply managing the pain and start addressing the fire that starts it.

¹(Ferretti, A., Gatto, M., Velardi, M., Di Nardo, G., Foiadelli, T., Terrin, G., Cecili, M., Raucci, U., Valeriani, M., & Parisi, P. (2023). Migraine, Allergy, and Histamine: Is There a Link?. Journal of Clinical Medicine, 12(10), 3566. https://doi.org/10.3390/jcm12103566) 

Let us know! Do you think histamine is impacting your migraine symptoms? Have you been diagnosed with histamine intolerance or MCAS?