If you have Histamine Intolerance or Mast Cell Activation Syndrome, you may be wondering if antihistamines can help.  And you might also wonder what the best antihistamine for Histamine Intolerance (HIT) is?

Or if there is a best antihistamine for Mast Cell Activation Syndrome (MCAS)?

You’re not alone, we get a lot of questions on these topics. 

And the answer is that antihistamines can be part of the solution AND part of the problem!

So, it’s important to know why. 

Keep reading to learn more about:   

• What antihistamines are 
• Why antihistamines can be helpful 
• The best antihistamine for Histamine Intolerance and MCAS
• Natural antihistamine supports
• Seeing the bigger picture to help get your health back 

Now, let’s take a closer look at Histamine Intolerance and antihistamines! 

It’s important you know that this blog post is for informational and educational purposes. It’s not meant to treat any health condition or to be prescriptive for anyone.  If you have any medical condition, it is critical you work under the care and guidance of a licensed medical provider.   

What Is Histamine Intolerance? 

Histamine is a type of chemical called an amine.    

It can come from the foods you eat. Some histamine-rich foods are things like aged cheeses, fermented food (sauerkraut, yogurt), aged beef, or salami. 

And your mast cells make histamine, too.  

Your body will always make some histamine, and that’s a good thing!  

Histamine is part of many necessary processes.

But for some people, histamine levels build-up because they aren’t processing histamine fast enough. 

And that’s when you get Histamine Intolerance (HIT).  

Related Article: What is Histamine Intolerance?  

Symptoms of Histamine Intolerance 

These are a few of the common symptoms of Histamine Intolerance: 

• Itchy, red, watering eyes
• Fatigue
• Insomnia

Respiratory symptoms:  

• Congestion
• Coughing 
• Shortness of breath 
• Wheezing 
• Runny nose 
• Sneezing  

Gastrointestinal symptoms (related to the gut):  

• Nausea 
• Vomiting 
• Diarrhea  

Skin-related symptoms:  

• Itching 
• Hives (Urticaria) 
• Rashes 
• Eczema 

Next, let’s talk about how antihistamines can help with histamine reaction symptoms.  

How Antihistamines Work for Histamine Intolerance 

Here’s how antihistamines work.  

Cells, including mast cells, get information through receptors. Receptors are just proteins on a cell’s surface that bind to specific molecules. 

These receptors respond to things in your environment like: 

• Environmental allergens
• Temperature
• Scents
• And more   

And they respond to what’s happening within your body. This could be things like: 

• Viruses
• Bacteria
• Foods you eat
• Or more 

Among these many types of receptors, there are 4 known histamine receptors – H1, H2, H3, and H4. And these receptors regulate the release of histamine.   

Antihistamines block some of these receptors from communicating with the cell and the rest of your body.

So, they stop some of the activity of histamine.  

That doesn’t mean the histamine is gone. Your body still needs to break down and eliminate what’s there. But it can help ease symptoms. 

And it can help with MCAS, too! Keep reading to learn why. 

Why Antihistamines Can Be Helpful for MCAS 

Not everyone with Histamine Intolerance (HIT) has Mast Cell Activation Syndrome (MCAS). And not everybody with MCAS has HIT. But, in the clinic, we find most clients with MCAS also have HIT. 

So, why would antihistamines help if you have both? 

Well, you just read about receptors. And mast cells have hundreds of them. Histamine is one of those receptors. Which means histamine can trigger mast cells! 

And when they are triggered, mast cells can release even more histamine. Which triggers more mast cells. And around it goes.  

You can see how this can become a problem. And how blocking histamine can help calm down mast cells.  

And calm mast cells can mean less histamine. 

So, what do you do about it? 

Depending on the severity of your case, you may need over-the-counter (OTC) or prescription antihistamines to help quiet your histamine response and mast cell flares.

Others may find that mast cell stabilizing supplements are enough.

So, let’s look at histamine and mast cell supports you may want to talk with your practitioner about.  

What is the Best Antihistamine for Histamine Intolerance and Mast Cell Activation Syndrome? 

That’s the million-dollar question!   

Truly, everyone is unique in what will be the best.

That’s why it’s always so important to talk with your provider who knows your case history to determine the best antihistamine for you.  

Let’s take a look at some options you may want to discuss.

The Best Antihistamine for Histamine Intolerance: H1 Blockers

Remember you read earlier that there are 4 types of histamine receptors? 

H1 antihistamines work by blocking H1 receptors in the body. These receptors play a major role in inflammation and allergy type symptoms.   

H1 receptors signal histamine release. And histamine release leads to symptoms.  

H1 receptors are found on or in your:  

• Mast cells
• Nervous system 
• Lungs 
• Skin 
• Liver 
• Cardiovascular system 
• Various other immune cells

That’s why H1 blockers can help with many different types of allergy symptoms, seasonal allergies, and Histamine Intolerance symptoms.

You can get both over-the-counter (OTC) and prescription H1 blockers. And for some, OTC antihistamines are enough. Others will need prescriptions.

Let’s take a closer look at what some of those are.

It’s important you know that this blog post is for informational and educational purposes. It’s not meant to treat any health condition or to be prescriptive for anyone.  If you have any medical condition, it is critical you work under the care and guidance of a licensed medical provider.   

Second Generation Antihistamines and Ketotifen 

Second generation H1 antihistamines have been shown to have longer duration than first generation antihistamines. They work longer so you don’t have to take as much. 

Second generation antihistamines have also been shown to be safer for long term use. And safer in terms of drug interactions, too.  

But you should still always talk with your provider or pharmacist before starting anything new. 

First generation antihistamines are drugs like:  

• Diphenhydramine (Benadryl)
• Doxylamine (Tylenol Cold and Cough Nighttime) 
• Brompheniramine (Dimetapp) 
• Hydroxyzine (Atarax)   

Second generation antihistamines are drugs like:  

• Loratadine (Claritin) 
• Fexofenadine (Allegra) 
• Cetirizine (Zyrtec) 
• Levocetirizine (Xyzal)  

Ketotifen is also a second generation antihistamine.  

But unlike the other second generation H1 antihistamines, ketotifen has mast cell stabilizing properties, too! 

So, if other antihistamines haven’t been enough. You might consider talking with your practitioner about ketotifen. 

In the US, ketotifen is only available as an eye drop at the store. So, you will need a prescription to get this medication for oral use through a compounding pharmacy (more on that below).

It’s frequently used to also help with:  

• Food intolerances 
• Hives 
• Sleep  
• Asthma 

Because ketotifen stabilizes mast cells, they release less histamine. So, this also helps with HIT.   

Remember, with Histamine Intolerance, your body has more histamine than it can deal with. And one of the main ways you address it is by reducing your histamine load.   

Another mast cell stabilizing medication we often get asked about is Cromolyn Sodium (Gastrocrom). Let’s take a quick look at that.  

Cromolyn Sodium 

While cromolyn sodium is not an antihistamine, it is commonly used as a mast cell stabilizer for MCAS when antihistamines are not enough.  

As a stabilizer, it works by preventing mast cells from releasing mediators like histamine, particularly in the gut.  

It works well for some people. However, it can be challenging to onboard and can have some significant side effects for others, like abdominal pain and nausea.  

Another major drawback can be the cost. If insurance doesn’t cover it, even the generic version may be hundreds of dollars a month.  

H2 antihistamines can also play a role in blocking histamine and stabilizing mast cells, especially in the gut. Let’s look at those next.

The Best Antihistamine for Histamine Intolerance: H2 Blockers   

H2 antihistamines work like the H1 antihistamines, by blocking histamine receptors.  

H2 receptors are found in high numbers along your whole gut.  

That’s why you can get a lot of histamine related gut issues. 

H2 blockers can be helpful for their use in digestive related symptoms like:  

• Heartburn  
• Acid reflux 
• Diarrhea 
• Mast cell related food sensitivities 
• And more 

H2 receptors are also found in the:  

• Urinary system 
• Uterus 
• Skin 
• Respiratory system  

So, H2 blockers may help with symptoms related to those systems and organs, too. 

Here’s something that often gets confusing about H2 blockers and proton pump inhibitors (PPIs).  

H2 blockers are drugs like:  

• Famotidine (Pepcid AC)    

PPIs are drugs like:  

• Omeprazole (Prilosec)
• Pantoprazole (Protonix)  

Both can help with the gastrointestinal tract (gut) related symptoms.  

PPIs work by blocking acid secretion in the stomach. 

But PPIs have a lot of serious downstream side effects when used long term.  

And a good number of Mast Cell 360 clients with gut issues have low stomach acid. That’s why PPIs aren’t always the best for those with MCAS-related gut issues. 

H2 blockers don’t reduce stomach acid directly and are much safer longer term than PPIs. And H2 blockers work differently.  

H1 and H2 antihistamines taken simultaneously can help reduce tissue inflammation caused by mast cell mediators.  

But some people prefer natural antihistamines or need layers of supports to stabilize. So, let’s look at some of the most helpful natural antihistamines we use with clients next. 

Natural Antihistamines 

These are some of the most commonly suggested antihistamine and mast cell supportive supplements in the clinic.  

DAO 

Did you know that digesting food causes histamine release? 

But if you have Histamine Intolerance, you want to be sure to support the breakdown of histamine in your body.  

And DAO enzymes (diamine oxidase) break down histamine.   

Taking a DAO supplement like Histamine Digest 360 DAO can help.   

DAO may be the best “natural antihistamine” because it actually reduces histamine in the body.   

Related Article: Diamine Oxidase (DAO) for Mast Cell Activation Syndrome or Histamine Intolerance   

Perilla Seed Extract

Perilla seed extract is an herb that has some wonderful histamine lowering, mast cell calming, immune supporting, and anti-inflammatory properties.

Studies have also shown perilla can be effective in calming allergic responses and soothing symptoms like: 

• Itching
• Swelling
• Sinus congestion

One of our favorites is Perilla Seed Extract

Quercetin 

Quercetin is a natural bioflavonoid known for its strong antihistamine and anti-inflammatory properties. This makes it a great option for those with both Histamine Intolerance and Mast Cell Activation Syndrome.  

Some of the potential benefits of quercetin are: 

• Mast cell stabilizing
• Histamine lowering
• Anti-inflammatory
• Overall immune support 

Our favorite quercetin is Alpha-Glycosyl Isoquercitrin. This is a highly bioavailable (absorbs easily) form, so you need less of it.  

Related Post – with low salicylate options: The Best Quercetin Supplements

Baikalin 

Chinese Skullcap (Scutellaria baicalensis) is another herb known for its antihistamine and mast cell stabilizing properties. You might see it called baicalin or baikalin.  

It’s important to note that Chinese Skullcap is different than American Skullcap (Scutellaria lateriflora), so be sure to check the label carefully. 

Some of the potential benefits of Chinese Skullcap are: 

• Mast cell stabilizing
• Histamine lowering
• Anti-inflammatory
• Neuroprotective
• Anxiety reducing 

Our favorite Baikalin / Chinese Skullcap is: 

Other Natural Antihistamine Support 

Here are a few other potential histamine supports:

• Water – hydration is important 
• Baking Soda 
• Gotu Kola Tea 
• Pekana Inflamyar (topical) 
• Histaminum (homeopathic) 
• AllQlear – may also help lower tryptase levels 
• SPM Supreme 

Learn more in the Top 8 Mast Cell Supporting Supplements Master Class, including troubleshooting sensitivities when you try new things.

The Best Antihistamine: Supplements vs Medications

If you really struggle with severe symptoms. 

And you still need a way to get your MCAS or HIT symptoms under control.  

Or if you have Salicylate Intolerance and herbal supplements aren’t well tolerated. 

Medications are often part of the solution in these cases. 

Antihistamines and other mast cell medications are absolutely essential for some people.  

But many people with MCAS struggle to tolerate any supplements or medications. Keep reading for a few helpful tips. 

Challenges of Choosing the Right Antihistamine with MCAS 

It may feel like you react to everything! And if that’s the case, nervous system rebooting can be a good place to start. 

Here are a few other things for you to consider. 

What or How Much to Take: Individual Responses and MCAS 

Each person is different in what they tolerate. And what they need. That’s why you should speak with your provider to figure out what is best for you.   

You can also talk with your provider about starting “low and slow.” 

Starting with too much, even though it’s a regular dose, can backfire when you’re sensitive.  

So, in the Mast Cell 360 Clinic, we often suggest starting most things with just drops or sprinkles. And going slowly.

This often makes a difference in what people can tolerate! 

Learn more about onboarding supports when you’re sensitive from this video: 

Another thing to note is that there can be mast cell triggers and high histamine ingredients in some otherwise helpful supplements or medications. Here’s what to know about that.  

Sensitivities to Fillers and Ingredients with MCAS 

Supplements, prescriptions, and over-the-counter medications may all contain ingredients that are common triggers for MCAS or HIT. 

For some people, these small amounts won’t make a noticeable difference. But for others, they will.  

If you are sensitive, you want to watch for:   

• Artificial colors 
• Artificial flavors  
• Corn starch
• Dyes 
• Titanium Dioxide 
• Potassium Sorbate
• Sodium Benzoate 
• Citric Acid  
• Citrates 
• Sodium Triphosphate  
• Potassium Triphosphate 
• Talc 
• Ascorbic Acid 
• Ascorbyl Palmitate
• Clove or cinnamon
• Citrus oils 

Not everyone will have trouble with every one of these.  

But, generally, the best antihistamine for Histamine Intolerance, and especially Mast Cell Activation Syndrome, will avoid these ingredients. 

Buying clean, high-quality supplements with few ingredients can also help. 

And if you’re still struggling to tolerate medications, there is one more option.

 
Compounded Medications 

If you are sensitive to over the counter or prescription medications, you can also talk with your provider about getting your medication compounded.  

This means you will get to choose a filler you tolerate. 

Work with your practitioner and compounding pharmacist to find a filler that works well for you.  

Some examples of fillers are: 

• Avicel / cellulose
• Baking soda
• Distilled water – can be helpful for really sensitive people (not all pharmacies will do this, you might have to call around)

But, as you read earlier, just finding antihistamines that help symptoms isn’t where you want to stop. Lowering symptoms is not the same as healing.  

To heal, you want to find and address your root causes! 

A Root Cause Approach to Histamine Intolerance and MCAS 

Antihistamines can provide the relief you need. And when used alongside addressing root causes, they can really help you to rest and heal.  

The key is to look at antihistamines as part of the solution. Not the whole solution.  

Many doctors don’t know about Mast Cell Activation Syndrome or Histamine Intolerance.  

A lot of symptoms of MCAS and HIT look like allergic reactions. Or asthma.   

So, doctors do what they know to do. Treat the symptoms.  

Just focusing on symptoms doesn’t consider why your symptoms are happening. And if you stop taking the antihistamines, the symptoms will come back. That’s why you want to address your root causes!

Let’s look at how to heal next.

Why You Also Want to Address Root Causes While Using the Best Antihistamine for Mast Cell Activation Syndrome and Histamine Intolerance

Root causes are the big underlying issues behind your symptoms.  

Think of root causes like a tree.  

The leaves are the symptoms. Symptoms are the part you notice. They are the showy leaves aka the sneezing, itching, and headaches.  

Leaves stem from branches.  

Like the leaves, your symptoms stem from something. In this case the symptoms are coming from Mast Cell Activation Syndrome (MCAS) and Histamine Intolerance (HIT).

Underneath it all, you still have the roots. That’s the base everything else grows from. These are what we call the root causes of MCAS and HIT.  

If you only treat the leaves (the symptoms), your tree may look better for a time.   

But once you quit treating the leaves, the problem is going to come back.  

That’s because the problem started in the roots. And you didn’t address the roots. Only the leaves.  

When antihistamines are your only solution, you’ll likely be on them long-term.  

And in the long-term here’s what you might expect:  

• Worsening side-effects 
• Developing a tolerance – you need more to see results
• Chemical dependency  
• Continued illness

It doesn’t have to be that way, though. Especially with the advances in understanding and medicine that are seen every day.  

But you do need to look at the big picture…the root causes.  

Common Root Causes of Histamine Intolerance and Mast Cell Activation Syndrome 

So, what are your root causes?

It’s not usually just one thing.  

Here are some of the most common root causes our practitioners work with clients on. So, you have fewer symptoms AND your body can start healing: 

• Nervous system dysregulation (vagal and limbic)
• Mold Toxicity
• Food intolerances – like low histamine diet
• Chronic infections – like Lyme, Bartonella, Babesia, viruses
• Environmental Toxins
  • Clean air
  • Clean water
  • Clean beauty/personal care products
• Gut issues – like Leaky Gut, SIBO, and SIFO 

And that’s just a few. 

With MCAS and Histamine Intolerance, looking at the big picture helps!  

And antihistamines can be one part of that picture. But by addressing your root causes, you often reduce or even entirely remove your need for medications.

What has been the best antihistamine for Histamine Intolerance or Mast Cell Activation Syndrome for you? 

Learn More About HIT and MCAS  

• What is MCAS?  
• What Is Histamine Intolerance?
• Do You Have One or Both? Histamine Intolerance vs Mast Cell Activation Syndrome 
• Mast Cell Foundations: Mediators and Receptors
• Low Histamine Diet Plan 

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