Mast Cell Activation Syndrome

by Jacob Teitelbaum MD) from the book From Fatigued to Fantastic (Penguin June 15, 2021) and You Can Heal from Long Covid (June 2024)

Mast cells are our body’s first responders when contacting things in the outside world. If they meet something in the environment that concerns them, they can pour out over two hundred chemicals. The most prominent of these is histamine. This is one reason why antihistamines are a mainstay of treating allergies.

Just like our immune system in fibromyalgia can be on overdrive, in some people this is also occurring for their mast cells. These guardians then have an itchy trigger finger, seemingly reacting to things at random.

“Random” is the key word here, and this helps distinguish mast cell activation from regular allergies and sensitivities. One day you may have no reaction to something, but you react excessively to the same trigger on other days. So, no problem eating an ear of corn one day. But the next day, you have may have the sudden onset of flushing, nausea, diarrhea, sweating, or palpitations.

Interestingly, most of the brain’s histamine is located in the hypothalamus. Also, mast cells are also found in the pituitary and other glands. Because of this Dr. Theoharis Theoharides, one of the main researchers on mast cell activation, theorizes that this may be a major trigger for many people with CFS/FMS. The mast cells may then be a major trigger for microglial cells pouring out inflammatory factors (central sensitization) even in response to minimal stress.

Testing

Testing is usually not helpful for this condition. As about half of fibro folks with sensitivities have mast cell activation syndrome, and treatment is simple, so it’s better to simply try these and see if they help.

Treatment

I usually begin in the following order:

1. Quercetin

Quercetin is a bioflavonoid is a cousin to vitamin C. It helps stabilize the mast cells, a bit like calming down and soothing a crying baby. I start with 500 mg once a day. If your main sensitivities are to foods, you should take it about 30 minutes before major meals so it can be in your system when you eat. This simple supplement can often be very helpful, is inexpensive, and can be found in any health-food store. After a few days, you can increase to 500 mg (or even 1,000 milligrams) 2-4 times daily. I recommend Terry Naturally’s Quercetin with Vitamin C as it provides markedly enhanced absorption.

Quercetin is a bioflavonoid and a cousin to vitamin C. It helps stabilize the mast cells, a bit like calming down and soothing a crying baby. I recommend the Terry Naturally Quercetin with Vitamin C (200 mg), 1 a day. If your main sensitivities are to foods, you should take it about 30 minutes before major meals so it can be in your system when you eat. After a few days, you can increase to 1-2 capsules 2-4 times daily. Quercetin with Vitamin C provides markedly enhanced absorption. I find one of these high absorption capsules to be better than 500 mg of regular quercetin.

2. PEA (Palmitoylethanolamide)

PEA directly settles down both mast cells and microglial activation. But it takes about 2-3 months to start working. However, it can help the entire pain, fatigue, and sensitivity process. Using the proper brand is critical because of absorption problems. I recommend the new “PEA Healthy Inflammation Response with Serratiopeptidase” supplement, which contains Gammasorb (an ingredient that aids absorption) as well. Take 2 capsules a night.

3.  Montelukast (Singulair®)

Take 10 mg at bedtime. This prescription asthma medication is only about $0.30 a day using the GoodRx phone app, and most physicians will be comfortable letting you try it. But one caution: Though quite uncommon, it can cause potentially extreme behavior- and mood-related changes. If that happens, you should stop taking it.

4.  Loratadine (Claritin®)

Take 10 mg of loratadine each morning. If this over-the-counter medication makes you drowsy, you can use it at bedtime or try 10 mg of cetirizine (Zyrtec)®. Doses over 20 mg are likely to be sedating. If you have any other side effects to these medications, it is likely caused by the binders or fillers rather than the medication itself. In that case, try a different brand or have it made by a compounding pharmacy without the fillers. If this medication helps, consider 12.5-50 mg of diphenhydramine (Benadryl®) at bedtime.

5. Acid-Blocking Medications

Some people will get additional benefits by adding 150 mg of ranitidine (Zantac) twice a day, 20 mg of famotidine (Pepcid®) twice a day, or even 150-300 mg of cimetidine (Tagamet®) twice a day. These acid-blocking medications are actually also antihistamines. Do not use the other acid-blocking medications (called PPIs). They will not help here and are quite toxic long term.

Cimetidine, famotidine, and ranitidine have the additional benefit of modifying immune function quite dramatically in ways that can be beneficial, especially against Epstein-Barr virus. In fact, I have seen cimetidine knock out acute cases of Epstein-Barr (mono) in less than 24 hours. This tip was taught to me by Dr. Jay Goldstein.

The downside is that they also turn off stomach acid production, and your body needs stomach acid to digest your food. The cimetidine can be the best choice of these three for long-term use in this regard, but see which one works best for you.

These medications may work within days, but Dr. Neil Nathan finds that it may take up to 2 months to see the full effect.

6. DAO (Umbrellux™)

Taking a DAO supplement 15-30 minutes before eating can be helpful, but it costs about a dollar per capsule. DAO contains the enzyme diamine oxidase, which helps break down histamine. Start by taking 1 capsule 30 minutes before a meal, and increase to 2-3 capsules as you find needed.

7. Cromolyn (Gastrocrom®) Ampoules

Taking 1 ampoule (100 mg/5 mL) before each meal can be quite effective for histamine reactions from food, but this is often not insurance covered. With the GoodRx app, they are about a $1.60 per ampoule.

8. Low-Histamine Diet

In persistently severe cases, consider a low histamine diet. Information can be found online, but this is quite a nuisance and I rarely use it.

In some, the severe sensitivities require addressing the mind-body component as well. This has the benefit of not requiring taking any pills. Also, when accompanied by CFS/FMS and severe anxiety, mold toxicity is sometimes especially playing a key role. In another article at this website, "Sensitive to Everything," I discuss how to address these (much of this information comes from my dear friend and colleague, Dr. Neil Nathan, author of the book TOXIC).