compounding antihistamines for histamine intolerance

The Best Antihistamine for Histamine Intolerance and Mast Cell Activation Syndrome

If you have Histamine Intolerance and Mast Cell Activation Syndrome, you may be wondering if antihistamines can help. And if antihistamines can be helpful, you may be wondering what the best antihistamines for Histamine Intolerance are. 

Truth told, I had some problems with antihistamines at one time in my life. 

By the time I was 30, I found myself dependent on Benadryl (diphenhydramine).  

Benadryl is an antihistamine used for symptom relief and sleep. 

Did you know it’s common for people with MCAS and Histamine Intolerance to have sleep issues? That’s because mast cells and histamine play roles in the sleep/wake cycle. 

I took Benadryl every night for 4 years. 

If I accidentally skipped a night, I couldn’t sleep at all. 

And I itched so badly. I was terrified I’d gotten bed bugs somewhere. I’d wake up feeling like my skin was crawling. 

At some point, I realized I’d become dependent.  

It took me 9 months to wean off it.  

What’s worse is that I was just masking my problems with the Benadryl. It wasn’t really getting to the root causes. 

It was like putting a bandage on a broken arm. 

After hearing that story, you may be surprised that I recommend some people talk with their providers about taking antihistamines!  

What?! That’s right. And I’ll tell you why and what changed for me.  

Keep reading to learn more about:  

  • What antihistamines are 
  • Why antihistamines can be helpful 
  • The best antihistamines for Histamine Intolerance and MCAS I suggest talking with your provider about   
  • How you can support your histamine load with natural supplements  
  • The bigger picture that can help get your health back on track  

But first, let me tell you the rest of my story. 

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

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.   

The Rest of the Story 

Were you surprised that I still recommend antihistamines even after all the problems I had? 

In a way, I am too! 😀 

But here’s why. 

Yes, I had some bad experiences.   

But I’ve learned a lot since those early days when neither I nor my doctor knew what was really wrong with me.  

Antihistamines can really help if you have Histamine Intolerance or Mast Cell Activation Syndrome. 

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

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

In my case, I’d been on antihistamines off and on from the time I was a kid. 

My doctors didn’t know about Mast Cell Activation Syndrome or Histamine Intolerance. 

It turns out that a lot of symptoms of MCAS and HIT look like allergic reactions. Or asthma.  

So, my doctors did what they knew to do. Treat the symptoms. 

But nothing was known about root causes then. 

Root Causes 

What are root causes? They 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. 

Root causes are things like: 

That’s naming just a few.  

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. 

In my early days, I never got to my underlying conditions. I was only treating the symptoms over and over again.  

That’s a big chunk of the problem with antihistamines. They are offered up as the whole solution instead of part of the solution. 

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 (like what happened to me with Benadryl) 

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

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

Keep reading to learn more about how antihistamines fit into the bigger picture of regaining your health. 

The Pros of Antihistamines for Histamine Intolerance 

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

That’s right. Depending on the severity of your case, you may NEED them.  

Antihistamines and mast cell supporting medications are often necessary for people addressing root causes like Mold Toxicity and Lyme. 

These meds can keep MCAS from spiraling out of control.  

Another instance where medications can be very helpful is for people with Mast Cell Activation Syndrome (MCAS), Histamine Intolerance (HIT), and Salicylate Intolerance. 

With Salicylate Intolerance, tolerating herbal supplements can be a struggle.  

But you still need a way to get your symptoms of Histamine Intolerance and MCAS under control. 

Medications are often the solution in these cases. 

Like you read earlier, I’d been on medications almost my whole life. 

But once I learned about MCAS, HIT, and how to address my root causes, my experience with antihistamines changed. 

And the antihistamines themselves changed, too. Second generation antihistamines are safer than the first-generation antihistamines I’d been taking most of my young life. 

And some have mast cell stabilizing properties, too. 

Keep reading to learn more about that. But first, it may be helpful to review what Histamine Intolerance is and how antihistamines work. 

What is Histamine Intolerance? 

Histamine is a type of chemical called an amine.   

Histamine can come from the foods you eat. Your mast cells make histamine, too. 

For some people, the amount of histamine in the body builds up. This is because they aren’t processing histamine fast enough. 

That’s when you get Histamine Intolerance. 

Related Article: What is Histamine Intolerance? 

Histamine Intolerance is when your body can’t break down histamine as fast as it’s coming in.   

Symptoms of Histamine Intolerance can include: 

  • 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 

Antihistamines can help with these symptoms. Read more on that next. 

How Do Antihistamines Work?   

Antihistamines work to relieve some of those symptoms you just read about. 

Here’s how they work. 

Cells, including mast cells, get information through receptors.    

These receptors respond to your environment. This could be environmental allergens, temperature, scents, and more.  

And they respond to what’s happening within your body. This could be viruses, bacteria, and foods you eat, for instance.  

They are a very important part of your immune system. 

There are many types of receptors.  

Among these receptors, there are 4 known histamine receptors:   

  • H1 
  • H2 
  • H3 
  • H4 

These receptors regulate the release of histamine.  

Antihistamines block these receptors from communicating with the rest of the body. So, they block some of the activity histamine induces.  

Wouldn’t it be nice to not have to deal with aggravating symptoms every day? 

If you could start feeling better, you could put your energy elsewhere. 

You might have more energy for your family and friends. And you might have more energy for addressing the big picture of your health. 

Keep reading to learn more about the antihistamines you can talk with your doctor about. 

And you’ll read more about addressing root causes, too. 

What Are the Best Antihistamines for Histamine Intolerance? 

That’s the million-dollar question!  

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

Here’s some information you can talk with your provider about. 

H1 Blockers 

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

These receptors are what signal histamine release. And histamine release is what 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.  

One H1 blocker that I’ve had success with is ketotifen. 

It’s one I suggest my clients talk with their providers about, too.  

Here’s why. 


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

There have also been issues with long-term first generation antihistamines and cognition. 

Second generation antihistamines have 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 were 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 a second-generation antihistamine. 

It has mast cell stabilizing properties. 

And ketotifen has been shown to help with asthma due to its antihistamine properties. 

It’s frequently used to also help with: 

  • Food intolerances 
  • Hives 
  • Sleep  

For some people, the effects of ketotifen can be seen within minutes after taking it. And it can last for up to 12 hours.  

Ketotifen also stabilizes mast cells. Mast cells release histamine when triggered. This also helps with Histamine Intolerance.  

See, it’s actually preventing histamine from being released. This helps lower your histamine load. 

Remember, with Histamine Intolerance (HIT), your body has more histamine that it can deal with.  

And one of the main ways you address HIT is by reducing your histamine load. 

So, while ketotifen does help with symptoms, it’s not only addressing symptoms.  

It’s also helping to lower histamine levels by stabilizing mast cells.  

Next, let’s look at H2 blockers. 

H2 Blockers  

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

H2 blockers are drugs like: 

  • Ranitidine (Zantac)  
  • Famotidine (Pepcid AC)   

PPIs are drugs like: 

  • Omeprazole (Prilosec)  
  • Pantoprazole (Protonix) 

Both can help with GI (gastrointestinal aka gut) related symptoms. 

PPIs work by blocking acid secretion in the stomach.

And they are used for Barrett’s Esophagus. That’s a condition where there is damage to the esophagus (the tube that connects the mouth and 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 are much gentler than PPIs.  

They don’t reduce stomach acid directly and are much safer longer term than PPIs. 

And H2 blockers work differently. 

H2 blockers work like the H1 blockers by blocking the histamine receptors. 

H2 receptors are found in high numbers in the whole GI tract. 

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 receptors may help with symptoms related to those systems and organs, too. 

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

But here are a couple things you may need to consider if you have sensitivities. 

How Much Should You Take?  

This is a great question to talk with your licensed medical provider about. 

Your provider knows your health history and can help you with onboarding medications. 

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

In the Mast Cell 360 practice, we often say to start supplements with just drops or sprinkles. Then as tolerated, you can increase the amount. 

But each person is different in what they can tolerate. And what they need. 

That’s why you should speak with your provider to figure out what is best for you.  

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

Triggering Ingredients in Medications and What to Do About Them 

Both prescription and over-the-counter meds may contain ingredients that can be triggering. 

For some people, these small amounts won’t make a noticeable difference. But so many in our community are very sensitive.  

If you are sensitive, you want to watch out for:  

  • Artificial colors 
  • Artificial flavors 
  • Corn starch 
  • Dyes 
  • Potassium sorbate 
  • Sodium benzoate 
  • Talc 
  • Titanium dioxide 

But you can talk with your provider about getting medications compounded. This means you’ll get just the medicine without the fillers. 

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

Medications may be very helpful for you. But they should be part of the picture, not the whole picture.  

To really heal, you need to get to your root causes. You need to address the bigger underlying issues causing your Histamine Intolerance and MCAS.  

Sign up here to get your FREE REPORT on the 7 most common root causes of MCAS and how they may be affecting you. I’ll send it right to your inbox.

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Here’s more on that. And keep reading to learn about a supplement that can also help with your histamine load. 

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. 

Common Root Causes of MCAS and HIT 

Medications made a big difference for me once I got the right ones. And once I started using them while I was addressing my own root causes. 

Here are some of the most common root causes we see in the Mast Cell 360 practice. 

I was dealing with all of those. And I made some changes to really start healing.  

Here are some ways I did that. 

I was looking at the big picture. And the meds were one part of that picture. Not the whole picture. 

In addition to medications and lifestyle changes, supplements may also be helpful. 

One supplement that can help with Histamine Intolerance is DAO (diamine oxidase).  

Read more about that next. 

DAO (Diamine Oxidase) Supplements 

Some people are very sensitive. I happen to be one of those people. 

I’ve done a lot of work for my health. And I’ve made tons of progress. 

But I continue to support myself with natural supplements. This is part of how I look at the bigger picture of my health. 

If you have Histamine Intolerance, one reason your body may not be breaking down histamine fast enough is that you have low DAO (diamine oxidase) levels.  

DAO enzymes break down histamine.  

And vitamin B6 and a low histamine vitamin C help DAO work better.

Your body is always going to produce histamine. That’s actually a good thing. 

Histamine is important in: 

  • Digestion 
  • The sleep/wake cycle 
  • Immune response 

Did you know that even the act of digesting food causes histamine release? 

But if you are prone to Histamine Intolerance, you want to be sure to continue supporting the breakdown of histamine in your body. 

If your DAO levels are low, taking a DAO enzyme like the DAO supplement Histamine Digest 360 can help.  

Histamine Digest 360 Diamine Oxidase by Diem

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  

There are a lot of ways you can support yourself if you have Mast Cell Activation Syndrome and Histamine Intolerance. 

The best results often come when you start with the root causes and incorporate a big-picture approach to your health. 

Part of that big picture for you may be antihistamines. Consider talking with your provider to see what will be right for you! 

What has been the best antihistamine for Histamine Intolerance you’ve used? 

More on Histamine Intolerance and Mast Cell Activation Syndrome: 

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  1. Nancy Burkhalter

    I would love to have a printable PDF of the food list. Thanks. This is the most comprehensive information I have found on these topics. Thanks so much for posting.

    1. Suz, Mast Cell 360 Team

      Thanks so much for the feedback. We do anticipate having that out in the very near future.

  2. Harriet

    Thank you!
    I very much apreciate your clear and helpful postings.

    1. Jamie, Mast Cell 360 Team

      Hi Harriet, we are so glad you have found them helpful!

  3. DeeDee

    What strains of probiotics are best for histamine intolerance/MCAS????

    1. Kimberly

      I have struggled with Histamine intolerance for the past 9 years and the best supplement I have found is a histamine lowering probiotic from Smidge the sensitive formula (I order directly from their website). It has been life changing for me. I can now eat so many more foods and feel much better than I ever thought possible. Hope this helps:)

  4. Lacey

    I am confused about Ketotifen. When I google it, all I find are eye drops. Is this what you’re referring to? I’m not understanding how eye drops would help with asthma. Could you clarify this? Thank you!!

    1. Jamie, Mast Cell 360 Team

      Hi Lacey,
      Ketotifen can be compounded by a compounding pharmacy to take orally as well. You will need to speak with your licensed medical provider about a prescription and if it is right for you.

  5. Annette

    Thank you for this article! Can Ketoifen cause dependency, withdrawal or eventually cause you to have insomnia or rebound insomnia? A doctor recommended it and I’m all in if it can’t cause these things. Thank you kindly!

    1. Jamie, Mast Cell 360

      Hi Annette. You’ll want to discuss with your prescriber about possible side effects of any medicines. In our experience we have not seen these reactions but everyone can react differently to prescriptions.

  6. Wendy Bolt

    I got the kitotifen compounded. Cost me a bundle. It is just as strong as the over the counter drugs I tried. Too strong! Gave me fatigue and a drug hangover. I only took it twice. I’m sticking to my herbs, fenugreek and thyme combo. No unbearable side effects. I also cannot take benadryl. It makes me continuously dizzy. Ibuprofen makes me dizzy if I take it for more than a few days, like a week. Dizziness is the most common side effect with ibuprofen. At least it does not make me barf like aspirin used to to back in the day.

    1. Jamie, Mast Cell 360

      Hi Wendy, we’re sorry to hear that Ketotifen didn’t work for you. Everyone is so different and not everything will work for everyone. We love hearing that you listened to your body and have found what works best for you.

  7. Jim Jones

    I’ve been on ketotifen, famotidine and fexofenadine for about 6 weeks – unfortunately one of them (I suspect one or both of the first two) seems to cause urinary retention and repeated UTI/kidney infections

    A shame as it was really helping in terms of GI symptoms

    1. Jamie, Mast Cell 360

      Hi Jim, we are sorry to hear that you may be having a reaction to one of the medications. We recommend discussing your concerns with your licensed medical practitioner.

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