Histamine and Migraine: When Histamine Hurts or Helps Migraine Sufferers

A Guide to Histamine, Benadryl, and Migraines. This guide will break down everything you need to know about controlling migraines by controlling histamine.

Histamine and Migraine: When Histamine Hurts or Helps Migraine Sufferers.

A Guide to Histamine, Benadryl, and Migraines

There’s some confusion in the migraine community about whether histamine is a good thing or a bad thing. The truth is, it’s both: histamine may prevent or trigger migraines.

Histamine is a double-edged sword, which means anti-histamines such as Benadryl will both help or hurt migraine sufferers, depending on the situation. Don’t worry; there is a simple explanation that clears up the confusion.

This guide will break down everything you need to know about controlling migraines by controlling histamine.

Twelve Things You Should Know About Histamine

1. What is histamine?

Histamine plays a crucial role in maintaining neurotransmitters (study). It also plays a role in immune system responses and allergic reactions. You see, we need histamine in moderation but in excess it can become a problem.

2. When Too Much Histamine is a Problem

Your body absorbs histamine from a variety of natural foods to create the histamine needed for maintaining neurotransmitters and the immune system. However, processed foods with ultra-high levels of histamine are some of the most common migraine triggers.

These excessive levels of histamine can create the same type of immune system response as if you were allergic to something, from foods to dogs.

Migraine sufferers often become migraine free when going on a migraine diet that removes these common migraine food triggers that are rich in histamine. Here’s some proof.

3. What Foods Have a Ton of Histamine?

Aged meats, aged cheese, soy sauce, wine, and beer are a few of the most histamine-rich migraine triggers.

You don’t need to worry about natural foods with histamine, such as spinach, because they have relatively low levels of histamine and contain nutrients that prevent excessive amounts of histamine from forming in the blood.

Learn more about histamine foods here in a research-based migraine diet.

4. Dehydration and Migraines

Dehydration is one of the most common headache triggers, which can instantaneously trigger a migraine.

Histamine is released to stimulate thirst and likely plays a role in provoking dehydration migraines (study link).

5. Your Nose Hates Histamine and Migraines

Histamine is what activates your mast cells to open up your blood vessels and discharge snot, but also provokes sneezing, itching, and congestion (study).

Histamine is excellent when the body is trying to attack and expel foreign invaders, but it’s not so great when the body overreacts to things like pollen, dust, or harmless foods. An overreaction of the immune system is what we refer to as “allergies.”

The irritation that allergies cause in the sinus area can inflame the nerve associated with triggering migraines, which is called the trigeminal nerve.

Migraines triggered by the sinuses confuse doctors so much that a study by the New England Center for Headache found that 90 percent of sinus headaches are misdiagnosed and actually meet the criteria for migraine (study). The point is: irritating the sinus area is likely to trigger migraines.

According to a neurotoxin study published in the journal Toxicology and Industrial Health, “the better the inflammatory process is managed in the sinuses, the more easily migraines are managed” (study). We need to manage histamine to manage sinuses and migraine.

6. What Happens to Histamine and Migraines During Pregnancy?

Histamine goes away and so do migraines. Women have a 500-fold increase in diamine oxidase (DAO) during pregnancy. DAO is the primary enzyme for metabolizing histamine. Most women notice migraines disappear during pregnancy, with one study finding that migraines were eliminated entirely in 79% of pregnant migraineurs (study).

DAO takes histamine out of the blood where it may mimic allergic reactions. But the histamine doesn’t disappear. Much of the histamine is absorbed so that the cells can regulate neurotransmitters or use the histamine later as part of the immune system that protects the body (study).

Histamine is good and bad. It’s terrible when it builds up in the blood and triggers allergic reactions. However, when absorbed, the cells use histamine for basic health and to fight off migraines.

7. What About Migraine Genetics and Histamine?

A 2015 study published in the journal Headache found that a genetic defect in DAO production, which reduces its ability to break down histamine, may double a woman’s risk for migraines (study).

Reduced DAO function may result in various symptoms when someone eats processed foods rich in histamines, such as IBS symptoms, asthma, low blood pressure, and headaches. All of these conditions are associated with migraine.

Elevated histamine levels could also raise the body’s levels of inflammation and glutamate, which are two powerful migraine triggers (study).

Again, just like with pregnancy, DAO breaks down excessive amounts of histamine in the blood (which is bad) and lets the cells use the histamine for migraine prevention.

8. What is Benadryl?

Benadryl is an antihistamine that can help reduce the symptoms of allergic reaction or elevated levels of histamine in the blood. Theoretically, Benadryl should help lessen the migraines triggered by sinus problems, histamine-rich foods, or any types of allergies.

Many migraine sufferers combine Benadryl with other over the counter medications, some doctors prescribe Benadryl with other medicines, and many emergency departments use Benadryl as part of their migraine cocktails.

(Always consult your doctor before mixing any medications, even over the counter meds). 

9. Benadryl and Migraine Research

Despite Benadryl being one of our oldest medications and used by many migraine sufferers, there are no comprehensive studies for Benadryl and migraine.

Most of Benadryl’s migraine research is from Benadryl added to IV medications, but to reduce side effects and not necessarily treat migraine itself (study).

We need more research before we can conclude that Benadryl will help prevent or treat migraines for those migraine sufferers who are having problems with histamine. However, there are cases when blocking histamine could be a problem for migraine sufferers.

10. When is Benadryl a Migraine Trigger?

Large doses of Benadryl increase susceptibility to seizures (study). The San Francisco Bay Area Poison Control Center found that Benadryl accounted for about 7% of seizures associated with overdoses (research).

If excessive Benadryl triggers seizures, it will also trigger migraines in some sufferers, because both conditions share many of the same triggers.


11. A Migraine and Seizure Link

Migraines and seizures are both associated with overactive nerves that rapidly release glutamate and excite the neurons to death, also known as excitotoxicity.

Seizure medications treat both epilepsy and migraine by controlling the excitotoxicity that comes from overactive nerves and glutamate.

The question you should have, “why is an anti-histamine like Benadryl triggering seizures?”

12. Histamine, Excitotoxicity, and Migraine

While antihistamines are found to trigger seizures, histamine released by the neurons is found to block seizures (study). Histamine alleviates over-excited nerves by blocking the migraine trigger glutamate, which in turn reduces the excitotoxicity that may trigger seizures or migraines (study).

Controlling glutamate also reduces the migraine triggers of inflammation and oxidative stress, but we won’t get into those here.

To be clear, this research found that the histamine released inside of brain cells and the central nervous system is useful for migraine and seizure prevention. This is different from the excessive amounts of histamine in the blood from eating processed foods or the histamine released into the blood from mast cells, which stimulate allergic reactions.

Sum It Up

Too much histamine from foods or histamine released during allergic reactions wreak havoc on the body and may trigger migraines. In the case of allergies or drinking a couple of glasses of wine, an anti-histamine like Benadryl may prevent migraines. Benadryl is used by many migraine sufferers and may be helpful in moderation, but there are no studies to prove it.

Excessive use of Benadryl may block the histamine in the brain that is used to keep the nerves calm and prevent migraines and seizures. Histamine in the body plays multiple roles, so completely blocking all histamine will come with side effects. As with all migraine medications, long-term use may do more harm than good.

Medications only mask the symptoms of histamine. If you want natural solutions to long-term migraine prevention, I’ve got you covered with three natural bonus options below.

3 Natural Bonus Solutions 

1. Migraine Diet

Research-based migraine diets have been successful at eliminating migraines by reducing histamine-rich foods and inflammatory foods, which will reduce the histamine your body produces for the immune system.

The 3-day migraine diet

Diets are the best way to control the histamine response because they reduce the overall histamine response, but don’t block the histamine that your brain uses to prevent migraines. See my full diet here.

2. Ketones

We know that ketones prevent migraines by controlling overexcited nerves. The ketogenic diet, healthy fats, ketone supplements, or fasting produces ketones (full article).

New research published in the journal Nutrition and Metabolism also found that ketones control histamine released by the immune system response (study). This suggests that ketones help the histamine in the nervous system control overactive nerves from triggering migraines, while also preventing the histamine in the blood from causing an immune system response that would trigger migraines.

Remember that Benadryl only helps control the histamine released by the immune system or foods, and may increase migraine by eventually blocking the histamine needed by the nervous system. In stark contrast, ketones help control the nervous system and immune system.

3. Cannabinoids

The natural cannabinoid receptors in the human body help control histamine similarly to ketones. Stimulating the cannabinoid receptors prevents the release of histamine from an immune system response that you would get from overeating histamine-rich foods (study).

Stimulating the cannabinoid receptors also increases the histamine released in the brain, which may be why cannabinoids are incredibly potent at reducing the excitotoxicity found to trigger migraines and seizures (study).

For more on controlling migraines with cannabinoids, without getting “high,” read this article. Also, I have a book on how the natural endocannabinoid system controls migraine coming out soon.

Want to Learn More?

If you want to learn more about histamine, I recommend healinghistamine.com, which is written by an award-winning broadcast journalist, Yasmina, who covered war zones for the BBC. She now writes about natural solutions to histamine intolerance, which helped prevent her debilitating chronic migraines. Her writing is similar to that of this site because it’s all research-based and cited. (I have no affiliation, but I believe her site will be helpful for migraine sufferers with histamine intolerance.)


Author: Jeremy Orozco

Jeremy Orozco is a former firefighter turned migraine expert, author, and co-founder of MigraineKey.com. He's the author of Hemp for Migraine and The 3-Day Headache "Cure". You can find Jeremy here at MigraineKey.com and on Facebook. (See Jeremy's full bio.) // MigraineKey.com is dedicated to eliminating headaches and migraines. Forever. Share this post to help headache and migraine sufferers.

This is not medical advice, diagnosis, or treatment. Read the disclaimer.

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