Distinguishing Between Histamine Intolerance and MCAS

By Wayne Persky

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Those of us who have histamine sensitivity issues eventually become willing to try almost anything to stop the symptoms. Whether the symptoms are associated with digestive issues, or a rash or hives on our skin, they can eventually become maddening, and dominate our thoughts. The most obvious remedy usually appears to be to stop eating high histamine foods, or at least minimize their consumption. But what do we do when this isn't enough to stop the symptoms? What if the problems are a result of more than just a sensitivity to high histamine foods?

This article discusses the basic types of histamine problems, how to identify the specific type of issue that's causing the symptoms, treatment options available, and how to resolve the symptoms by using and orderly, systematic approach.

There are two basic possibilities.

1. Histamine intolerance (typically due to low DAO activity in the gut)
2. ​Mast Cell Activation Syndrome (MCAS), or a systemic histamine-related disorder

Histamine intolerance

is often caused by reduced diamine oxidase (DAO) enzyme activity, leading to an accumulation of dietary histamine.

• This tends to cause GI symptoms such as bloating, diarrhea, abdominal pain, or nausea.
• The symptoms appear after eating, and worsen after eating a meal that contains high histamine foods.
  
• Sometimes there will be flashing of the skin and mild itching, with occasional hives.
  
• Certain foods or wine may cause headaches, or even migraines.
  
• The symptoms usually appear within 30 minutes to two hours after eating.
  
• Triggers include high histamine foods, alcohol and fermented foods, for example.
  
• Symptoms are usually limited to the gut, skin, and head.DAO supplements may help significantly when taken 15 to 30 minutes before meals.

MCAS, or a systemic histamine-related disorder

tends to cause a chronic condition involving excessive histamine and other mediator release from mast cells throughout the body — not just the gut.

• At least two organs are affected (skin, gut, brain, cardiovascular, or respiratory).
• Skin symptoms can include flashing, hives, swelling, itching, and temperature sensitivity.
  
• Gut symptoms can be similar to histamine intolerance (diarrhea, bloating, pain, nausea, for example).
  
• Neurological symptoms can include brain fog, anxiety, irritability, for example.
  
• Cardiovascular symptoms can include dizziness, palpitations, low blood pressure, or near fainting.
  
• Respiratory symptoms can include nasal congestion, wheezing, throat tightness, for example.
  
• Triggers can include heat, stress, pressure (physical pressure can cause mast cell degranulation), exercise, foods, chemicals, insect stings, and even mosquito bites, for example.
  
• The onset of symptoms can be variable not always associated with food.
• Symptoms often improve in response to H1 and H2 antihistamines.
  
• The response to DAO supplements is often not enough, when used alone.
  
• Successful treatment may require antihistamines, mast cell stabilizers cromolyn sodium, or leukotriene blockers.

Consider these diagnostic clues:

• Food trigger only is common with histamine intolerance (HI), and often, but not always, with MCAS.
• Symptoms other than GI & skin are rare with HI, and common with MCAS.
• Flare-ups unrelated to meals are not typical with HI, but frequent with MCAS.
• Systemic allergic type reactions are rare with Hi, but can occur with MCAS.
• Antihistamines help only sometimes with HI, but frequently with MCAS.
• DAO supplements help often with HI, and often with MCAS, but are not sufficient.

When unsure:

• Keep a symptom/food log.
  
• Try a low-histamine diet for 2–3 weeks.
  
• Use DAO supplements before meals and see if symptoms improve.
  
• Trial an H1 antihistamine (for example, loratadine or cetirizine), and note improvements.
  
• Consider MCAS testing or consultation if symptoms are broad or severe.

Summarizing:

If your symptoms are mostly food-triggered and gut-centered, histamine intolerance is more likely, and DAO supplements may help. But if you have systemic, multisystem, or unpredictable flares, MCAS, or another mast cell disorder is more likely, and antihistamines, or a mast cell stabilizers will be needed.

Additional treatment information:

If histamine intolerance is the cause of symptoms, DAO supplements are readily available without a prescription, including online. In fact, a quick check shows that there are no DAO supplements that require a prescription. Just be sure to buy an enteric coated DAO supplement, because uncoated supplements will be degraded by stomach acid. While DAO supplements that are not enteric-coated may still be effective, enteric-coated supplements are typically significantly more effective, when they reach the small intestine, where they are needed.

MCAS treatment plans are much more complex,

and they may need to be developed under the supervision of a qualified healthcare provider. Developing a treatment plan for MCAS requires a step-by-step, layered approach, tailored to individual triggers, symptoms, and sensitivities. Similar to microscopic colitis (MC) there's no one-size-fits-all solution, but effective treatment generally involves a combination of avoidance, symptom control, stabilization, and nutritional support.
​

• After diagnosis, triggers should be identified, and avoided.
• Antihistamines should be introduced, by starting slowly, in order to avoid any undesirable reactions.
• H1 blockers, such as cetirizine, loratadine, fexofenadine, or hydroxyzine help to block itching, hives, and flashing.
• H2 blockers, such as famotidine help G.I. symptoms, nausea, and hypotension.Leukotriene blockers, such as montelukast zafirlukast help to prevent wheezing, brain fog, and GI system upset.

Mast cell stabilizers may be added to help prevent mast cell degranulation.

• Cromolyn sodium (Gastrocrom) is best for GI symptoms, usually at 4x/day dosing.
• Ketotifen (an H1 blocker plus stabilizer) is only available from compounding pharmacies in the U.S.
• Quercetin is a natural stabilizer that needs a high-dose, well-absorbed form.
• Luteolin is often paired with quercetin for enhanced effect.
• Vitamin C, D, and magnesium are cofactors with stabilizing potential.

​These agents are usually started one at a time, in order to monitor tolerance.

Nutritional and gut support should involve:

• Implementing a low-histamine or low-tyramine diet
  
• Treating SIBO, gut permeability, dysbiosis, if present
  
• Addressing nutrient deficiencies (for example, vitamin B12, B6, D, magnesium, iron, zinc)
  
• Considering DAO supplements before meals if histamine intolerance is suspected

Emergency preparedness for severe cases:

• Carry an EpiPen, especially if there’s a history of anaphylaxis or near-syncope (fainting).
  
• Have a rescue medication plan, such as diphenhydramine, (Benadryl) or prednisone.
  
• Wear a medical alert bracelet indicating MCAS.

Follow-up and adjust treatment regularly.

• Work with a knowledgeable provider (allergist, immunologist, or integrative MD).
  
• Adjust doses and treatments based on response.
  
• Consider evaluation for position orthostatic tachycardia syndrome (POTS), Ehlers-Danlos syndromes (EDS), or autoimmunity if symptoms overlap.

Remember:

• MCAS patients are often sensitive to additives, so dye-free, filler-free, or compounded medications may be needed.
  
• We may need to avoid synthetic fragrances, and volatile organic compounds (VOCs).
  
• Stress reduction such as, vagus nerve stimulation, and mindfulness can help reduce flare severity.

I'll share my personal experience:

Before I developed MC, similar to many of us, I used to love jalapenos and various other chilis, hot sauces, and fermented foods. Of course, they were no longer an option after I developed MC. After reaching remission, I continued to avoid spicy foods for a few years, and then I discovered that I could tolerate them again. So I began to eat jalapenos and picante sauce. And then I discovered sriracha.

I loved the flavor of sriracha, but it was my Waterloo.

As most people are probably aware, sriracha goes through extended fermentation,, and is rather spicy. Not much time passed before I realized that every time I ate a significant amount of sriracha, I developed severe itching. It promptly dawned on me that I was having excess histamine issues. And as the problem continued to escalate, various other relatively high histamine foods (that never bothered me before) suddenly began to cause an itchy rash, and hives, that began on my ankles, or the tops of my feet, and spread up my legs to the rest of my body, during the next few days.

For a few years I controlled the problem by avoiding (or limiting) high histamine foods in my diet, and this seemed to work well, except during hay fever season (I've had seasonal allergy issues all my life), when I would have to follow additional restrictions of high histamine foods (and even medium histamine foods) in my diet, to avoid urticaria problems. I keep my vitamin D level (25[OH]D) up around 60 ng/mL (150 nmol/L, and I take 300 mg of magnesium glycinate daily, divided between right after breakfast, right after lunch, and just before bedtime.​

But one day, the symptoms started, and wouldn't stop (reminiscent of MC).

A few months ago, I began to have regular histamine reactions, and restricting my diet even more tightly, seemed to help sometimes, but didn't usually adequately resolve the problem. I eat breakfast early, and my normal routine included two big slices of bacon, with sausage and eggs (wrapped in corn tortillas), for breakfast, followed by 2 cups of coffee (to kick my brain into gear), and get me going in the morning. About every other day, I would have a bowl of gluten-free (Chex) cereal for breakfast, and a bowl of only slightly spicy chili for brunch (Wick Fowler's 2 alarm chili, minus the red pepper).

For lunch, I would have either a length of pork sausage wrapped in a corn tortilla, and tortilla chips and Fritos, or pork country ribs, and steamed rice (with sugar and cinnamon). Since bacon, the seasonings in chili, and coffee, are high histamine foods, I tried cutting my "doses" of bacon and coffee in half, and eliminated the chili, with no apparent benefit.

I tried taking a DAO supplement

before every meal that contained any food that might cause histamine problems, and although I only developed slight areas of rash, the hives continued to appear daily and many of them were really aggravating. Some of them generated such intense itching that they would cause me to wake up in the wee hours of the morning, and make getting back to sleep, a difficult, and sometimes almost impossible, task.

A warm shower usually triggered an itchy rash on one or both ankles.

I had noticed that ever since my histamine issues first developed a few years ago, taking a shower with even slightly warm water would not only make the itching worse, but would sometimes cause areas of rash to appear that weren't there before the shower. And more recently, I noticed that my symptoms (hives, usually) didn't appear within 30 minutes to two hours of any meal — they appeared after the middle of the afternoon, during the hotter part of the day.

The handwriting on the wall was clear — I have MCAS.

It finally dawned on me that the basic problem wasn't due to food sensitivities (although it may have been initially, and some of it might still be). So the next morning, I stopped taking the DAO supplements, and began taking fexofenadine (Allegra), a 24 hour antihistamine tablet. To verify that this overdue realization was correct, I went back to two big slices of bacon with breakfast, and 2 cups of coffee.

Voilà.

My skin remained free of hives not only during the heat of the afternoon, but until the next morning, when it was time to take another antihistamine tablet. Late that afternoon, I got so hot mowing weeds that there wasn't a dry stitch left in my clothing, and I had no itching. When I took a shower that night, only a few left over hives (from previous days' reactions) made a feeble attempt to itch. If I woke up during the night, I don't remember, but I definitely was not awakened by any itching. Within four days, I was eating chili again. Problem solved.

I'm probably fortunate.

So I was apparently lucky — a single antihistamine tablet per day resolves my symptoms, at least for the present. If symptoms show up in the future, I'll double the dose. Note that under professional care, it's generally safe to take up to four antihistamine tablets per day, but I wouldn't attempt that without professional oversight. And the next step, if symptoms should return after that, would be adding Gastrocrom. It's great to finally be symptom-free.

So based on my experiences, it appears that I am indeed sensitive to high histamine foods, but I got to a point where avoiding high histamine foods, did not reliably prevent-reactions, and even adding a DAO supplement didn't seem to help. But taking an antihistamine daily prevents any symptoms. Note that this doesn't mean that I can just eat anything I want, but as long as I limit my intake (of high histamine foods) to the levels that were previously safe (a few months ago, before the recent problems began), I remain symptom-free.