Histamine 101: What You Need to Know About Histamine Intolerance

Runny nose? Sneezing? Itchy, watery, red eyes? All of these are familiar signs you might associate with seasonal allergies. If you suffer from seasonal allergies like clockwork, you may have been advised to take antihistamines to relieve your symptoms. 

But the effects of histamine aren’t just limited to typical allergy symptoms — we’re learning that histamine has diverse and far-reaching effects on your health.

In this article, we’ll delve deep into what histamine is and how histamine intolerance could be the culprit behind your nagging symptoms.

What is Histamine?

Histamine is a type of chemical called a biogenic amine naturally found in all tissues of your body. It’s created and stored in high concentrations in various types of white blood cells, though primarily in the cells called basophils and mast cells. 

When basophils and mast cells detect what they believe is a potentially harmful substance (an allergen), they release histamine and other chemicals into your bloodstream. 

Once free, histamines increase the immune system’s attention to the affected area by dilating the surrounding blood vessels and increasing their permeability. These actions allow your white blood cell artillery to migrate to the site of injury or infection. 

In addition to blood vessel dilation, histamine plays a role in:^1,2

• Inflammation
• Stomach acid secretion
• Smooth muscle cell contraction
• Cytokine (signaling molecule) production
• Regulation of your immune system
• Wound healing
• Your day-night rhythm

Additionally, histamines act as neurotransmitters, carrying chemical signals from one brain cell to its target. 

These wide-ranging effects occur through interactions between histamine and the four types of histamine receptors (H1, H2, H3, and H4). These histamine receptors are distributed throughout your body.³

Simply put, histamine’s involvement in your body is much more dynamic and profound than what many people are aware of.

Histamine Metabolism: How Your Body Breaks Down Histamine

Your body breaks down histamine in two known pathways involving the enzymes diamine oxidase (DAO) and histamine-N-methyltransferase (HNMT). 

The activities of DAO are restricted to certain tissues, mainly your small intestine, ascending colon, placenta, and kidneys.⁴ DAO is responsible for the breaking down of histamine located outside your cells, such as those from food.⁵

In contrast, HNMT can be found in many more tissues in the human body, including your:⁶

• Kidneys
• Liver
• Spleen
• Colon
• Prostate
• Ovaries
• Spinal cord cells
• Trachea
• Gastrointestinal tract
• Respiratory tract

Unlike DAO, HNMT inactivates histamine inside your cells.⁷

A disproportionate amount of histamine in your body is thought to come from eating histamine-containing foods or drinks, or from consuming substances that cause histamine to be released.⁸ 

For that reason, while HNMT and DAO are both found in the gut, DAO plays a much more significant role in protecting your body from ingested histamine.⁹ 

And research shows that an impaired degradation by DAO is the primary cause of histamine intolerance.^10,11 We’ll discuss this further in the sections below.

What is Histamine Intolerance?

“Histamine intolerance” may suggest a sensitivity to histamine. 

But the phrase is a bit misleading. 

Histamine intolerance isn’t an issue of sensitivity or allergy – rather, it’s a “non-allergic adverse reaction to ingested food.”¹²

In other words, histamine intolerance means that your body produces too much histamine in response to certain foods and drinks and can’t break it down. 

Think of your histamine levels as water in a cup. Your body (the cup) can handle histamine levels up to a certain point. But when the levels get too high, the cup overflows. The overflowing water and the resulting mess can be thought of as the negative symptoms of histamine intolerance. 

Symptoms of Histamine Intolerance

Symptoms of histamine intolerance are multifaceted and can manifest in multiple organs. Many of the symptoms mimic those of allergies, and include:^13,14,15

• Stomach issues
• Nasal congestion, sneezing
• Headaches and migraines
• Severe menstrual cramps and pelvic pain, abnormal menstrual cycle
• Weak muscle tone
• Irregular heartbeat
• Flushing (especially with alcohol, most notably red wine)
• Asthma
• Fatigue
• Nausea and/or vomiting
• Fluctuating body temperature
• Anxiety/irritability
• Difficulty falling asleep, easily aroused
• High blood pressure (hypertension)
• Vertigo, dizziness
• Hives

As you can see, the symptoms of histamine intolerance are broad and nonspecific, meaning they could be symptoms of many other illnesses. 

It’s no wonder that obtaining a diagnosis of histamine intolerance can be time-consuming and frustrating.

What Causes Histamine Intolerance?

Different mechanisms have been proposed as the cause of histamine intolerance. 

The most widely accepted model is that histamine intolerance results from both an increased availability of histamine and an impaired histamine degradation pathway. 

As mentioned above, DAO functions as the first defense against too much histamine building up in the GI tract by breaking down excess histamine.

This means that when there is a deficiency in DAO or if its function is impaired somehow, histamine can accumulate in your body.¹⁶ Increased amounts of histamine can also block HNMT activities.¹⁷

So what causes a DAO deficiency?

Research suggests DAO activity can be used as a good indicator to assess the integrity of your intestinal lining. For example, in inflammatory bowel diseases, the reduction of DAO activity has been shown to be related to the degree of intestinal barrier damage.¹⁸

This means that anything that can damage the surface of the intestinal lining may affect DAO levels, such as:

• Leaky gut¹⁹
• Medications, such as metronidazole²⁰
• Competition by other biogenic amines²¹
• Gastrointestinal diseases²²
• Alcohol use²³
• Gluten intolerance²⁴
• Disorders associated with mast cells²⁵
• Imbalance in your gut microbiome²⁶

Use of histamine modifying agents can also affect DAO production or function. Examples of these include:²⁷

• Antihistamines, like Allegra and Benadryl
• H2 receptor blockers, like Tagamet and Pepcid
• Antidepressants, like Cymbalta and Prozac
• Antiarrhythmics, like Propranolol and Norvasc
• Immune modulators, like Humira and Plaquenil

Certain genetic variants can also decrease your body’s ability to break down histamine.²⁸

What About Antihistamines Like Claritin or Zyrtec?

Antihistamines like Claritin and Zyrtec are common go-to solutions for people with seasonal allergies. 

So can they help if you have histamine intolerance?

Antihistamines work by blocking certain histamine receptors. By doing so, they’re able to prevent the usual symptom cascade of sneezing and watery, red eyes. 

Unfortunately, antihistamines don’t change the amount of histamine released by your body – just the symptoms you experience. 

And because histamine normally has such a stimulating effect, you may feel tired or fatigued when taking antihistamines.

And as mentioned above, antihistamines can actually negatively impact your natural DAO level production  – this is why considering other mast cell stabilizing supplements long term or sublingual immunotherapy is something you & your MaxWell Care clinician can discuss 

MaxWell Clinic’s 5-Step Approach to Histamine Intolerance Treatment

So you think you might have histamine intolerance…now what? 

Despite significant advances made in the understanding of histamine intolerance, healthcare experts have yet to reach a consensus on how to diagnose and treat it. 

Here’s how your MaxWell Care practitioner will approach your treatment:

1. Find the root cause: It’s critical to uncover the root cause of your histamine intolerance. Due to the complex nature of this condition, your MaxWell Care practitioner will need to know as much of your medical history as possible. This is so your practitioner can rule out food allergies or other gastrointestinal causes. Your practitioner may ask you a series of questions based on known symptoms related to locations of histamine receptors.

2. Remove high histamine foods: It’s impossible to eliminate all foods with histamine from your diet, but you may be able to reduce your histamine load by avoiding certain foods. High histamine foods include:

• Alcohol
• Fermented foods and beverages
• Vinegar-containing foods (olives, pickles)
• Dairy
• Dried fruit (raisins, apricots)
• Processed and cured meats
• Smoked fish
• Avocados (aged), spinach, and eggplants
• Shellfish

It’s also recommended that you avoid histamine liberators, or substances that have a histamine-releasing effect. These include:

• Alcohol
• Banana
• Chocolate
• Tomatoes, pineapples, strawberries, papaya, citrus fruits
• Gluten
• Walnuts, cashews, and peanuts

If you’re currently suffering from histamine intolerance, you may not have to avoid these foods forever. It can be a short-term solution until your histamine or DAO levels return to their optimal ranges. Depending on your unique situation, you may find that you tolerate some foods better than others.  

You might now be wondering – what can I eat? Here are some low histamine foods to enjoy:

• Fresh meat and freshly caught fish
• Non-citrus fruits
• Eggs
• Gluten-free grains, such as quinoa and rice
• Dairy substitutes, such as coconut milk and almond milk
• Fresh vegetables except tomatoes, avocados, spinach, and eggplant
• Cooking oils, such as olive oil

3. Heal the gut: Poor gut health creates a vicious cycle of producing more histamine and impairing your body’s ability to break it down. Repairing your gut may help reduce your overall histamine load and help keep it at healthy levels. 

Healing your gut is often a long-term task. Our goal is to heal tissue that’s being used all day every day. Your plan is personalized to your situation and needs, and may involve resting your gut and/or adding supplements. Your MaxWell Care practitioner will work closely with you and provide guidance so that your efforts to accomplish this aren’t wasted.

4. Add supplemental DAO: In addition to reducing your histamine intake, you can also improve your ability to break it down with a DAO supplement. We’ve seen excellent results with HistAID, our clinically tested formula that may dramatically reduce your symptoms. 

5. Consider supplementing with methyl donors to assist in the breakdown of histamine: Methylation is a biochemical process that involves the transfer of a methyl group between molecules. It’s required for numerous functions in your body, such as cell division, DNA and RNA synthesis, and histamine clearance. 

Because methylation is used for so many functions, one function can compete with others for methyl donors, resulting in methylation imbalance. 

The best methyl donor for supplementation is S-adenosyl-methionine, otherwise known as SAMe. This nutrient is also necessary for HNMT to break down histamine in your central nervous system. MaxWell Clinic offers SAM-e with Recharge Factor, a unique formula that is best absorbed under the tongue. 

Other methyl donors that may be useful are 5-methyltetrahydrofolate (5 MTHF), or methylcobalamin (methyl-B12). 

If supplementation might be helpful in your case, your MaxWell Care practitioner will discuss the proper form and dosing with you. 

Join MaxWell Care

If you suspect that you have histamine intolerance, it’s important that you work with a functional medicine provider. Treating histamine intolerance can be complex to diagnose and treat. 

That’s why we recommend our MaxWell Care program for patients with histamine intolerance. This 3- or 12-month program is designed to transform your health and quality of life by addressing your health concerns at the root. 

If you’re in the Nashville area and want to become a patient at MaxWell Clinic, we’d love to talk to you! Schedule your free 20-minute discovery call with our New Patient Coordinator to see how you can start your healing journey today.