Mast Cell Activation Syndrome in Infections & Mold Toxicity

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Mast Cell Activation Syndrome in a Lyme disease treatment image from Marty Ross MD

Updated 1/8/24 with a new video and new information on

  • KPV peptide and
  • low dose naltrexone.  

What is Mast Cell Activation Syndrome?

Are you reacting to a lot of things that you eat or take for your infections or toxicity? Are your environmental sensitivities or allergies getting worse? It could be Mast Cell Activation Syndrome (MCAS).

Mast cells are immune system cells found throughout the body. In the past, in medicine we thought they were only turned on to release histamines in allergic reactions. However we now know that they are turned on by a host of things like:

  • Lyme and other tick-borne infections,
  • Covid-19,
  • mold toxicity,
  • intestinal yeast overgrowth,
  • things that trigger allergies called allergens,
  • inflammation chemicals called cytokines,
  • drugs,
  • molds and fungae,
  • proteins,
  • toxins,
  • stress through an adrenal gland stimulating chemical called corticotropin releasing hormone (CRH),
  • and viruses.

Marty Ross Discusses Mast Cell Activation Syndrome 

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When Mast Cells become too turned on a person can have Mast Cell Activation Syndrome (MCAS). The chemicals released by activated mast cells include:

  • histamines,
  • inflammatory cytokines, prostaglandins and chemokines,
  • neurotransmitters like serotonin,
  • vasoactive chemicals like renin, and
  • hormone stimulators like VIP and CRH.

These mast cell chemicals effect many major organ systems in the body. So MCAS triggers an illness that can often look like other illnesses. And in some ways, like Lyme, it is a great masquerader.

Symptoms of Mast Cell Activation Syndrome

The symptoms of MCAS are due to the release of chemicals by activated mast cells. The symptoms of MCAS can include:

  • Body wide: fatigue, malaise, weight loss
  • Respiratory: nasal congestion, nasal itching, shortness of breath, throat swelling, wheezing
  • Neurologic: anxiety, depression, poor focus and memory, insomnia, migraines
  • Musculoskeletal: aches, bone pain, osteopenia, osteoporosis
  • Digestive: abdominal cramps, diarrhea, heart burn and reflux, nausea, vomiting
  • Skin: flushing, itching, hives, swelling of the skin
  • Cardiovascular: low blood pressure, fainting or near fainting, light headedness, racing heart.

Becoming More Allergic in Lyme

Many people with Lyme are allergic and reactive to many things in their environments. And for many with Lyme, this reactivity worsens during treatment. Lyme stimulates a variety of white blood cells including mast cells and T cells that attack Lyme to make cytokines. But research by Talkington and Nickell also shows when Lyme stimulates mast cells, it causes them to degranulate and release their histamines more easily. Degranulation and releasing of histamines is what happens in an allergic reaction when a person is exposed to an allergen like peanuts or pollens. But it now appears Lyme makes this whole process occur even when an allergen is not present. It might be possible that Lyme is turning on mast cells to be more sensitive to any and all allergens. 

Tests are Poor

There are a number of tests for MCAS, but generally they are very poor at identifying the illness. Blood tests include tryptase, histamine, prostaglandin D2 (PGD2), and heparin. There is also a urine test for PGD2 and n-methylhistamine. The best chance that these tests will be elevated is near the time someone is have an allergic reaction or when their allergic condition like asthma is active. PGD2 and heparin are very unstable, and break down easily so they must go to the lab chilled on ice after they are collected.

Do You Have MCAS?

MCAS is always a clinical diagnosis considering the signs and symptoms of the illness like allergy type symptoms and conditions, tests, and response to treatment. Because tests are very poor, I did not routinely do them in my Seattle practice and relied more on the signs and symptoms of someone being very allergic and improving with treatment.

Treatments for Mast Cell Activation Syndrome

1. Decrease Stress

Stress causes the brain to release CRH. CRH turns on the adrenal glands to help the body deal with stress. But CRH is a very strong stimulator of mast cells. Remove emotional toxins in your life and consider counseling, meditation, and exercise that help the body deal with stress.

2. Remove Allergens

If you have symptoms of allergies like runny nose, hives, asthma reaction, itching try to identify those things that trigger the reaction in your environment and with food. You may need the help of an allergist to identify these. For food, one way is to have your physician test for IGE antibodies against various foods. The immune system makes IGE antibodies against foods a person is allergic too. IGE antibodies bind to parts of the food a person is allergic too and then attach to the mast cells causing then to release histamines. If you cannot find a physician to help you, consider doing a food elimination diet that will help you identify foods you are allergic or sensitive to in any way. For more information see: Elimination Diet to Find Problem Foods. This article provides an elimination diet.

3. Treat Infections

As noted above, Lyme and other infections turn on mast cells. For information to help you figure out what infections you have see articles in How to Diagnose. And for treatment plans see articles in Infection Treatment Plans.

Pay particular attention to yeast overgrowth in your intestines. Yeast trigger excessive histamine release from mast cells lining the intestines. Read more articles on diagnosing and treating this problem in Yeast.

4. Remove Toxins

These toxins include chemical and even mold toxins. Two areas to consider in Lyme disease include MTHFR detoxification defects and Mold Toxin Illness. For more information see articles in Detoxification.

5. Lower Cytokines

As noted above, MCAS triggers the release of many chemicals by mast cells. One group of these are called cyotokines. Cytokines are responsible for many Lyme disease symtpoms. In excess they cause immune suppression. As a starting point use the supplement:

  • Liposomal Curcumin 500mg 1 pill 3 times a day.

You can also find other ways to lower cytokines in Control Cytokines: A Guide to Fix Lyme Symptoms & The Immune System.

6. Block Histamines and Allergic Inflammation

Histamines released by mast cells attach to a number of different histamine receptors. The two major ones are H1 and H2 receptors.

  • Antihistamines for H1 Receptors. Histamines attached to H1 receptors give most of the classic allergy symptoms like hives, itching, and runny noses. So if a person has symptoms related to H1 receptors use H1 receptor blockers like: Ketotifen, Benadryl, Zyrtec, Allegra, and Claritin.
  • Antihistamines for H2 Receptors. H2 receptors are primarily found in the stomach and intestines. Histamines that attach to H2 receptors give intestinal symptoms like nausea, diarrhea and abdominal pain.  If a person has symptoms related to H2 receptors then use H2 blockers like: Tagamet, Zantac, Prilosec, and Pepcid.
  • Leukotriene Inhibitors.To block inflammation in the airways and the nose use leukotriene inhibitors like: Singular and Accolate.

7. Stabilize Mast Cells & Moderate Immune System Effects of Allergens and Histamine*

Stabilize mast cells so they do not release their chemicals. There are a number of supplements people use for this, but the two best ones are:

  • Quercetin 250 mg 2 pills 2 or 3 times a day
  • Luteolin 100 mg 1 pill 2 or three times a day.

In addition to stabilizing mast cells, some herbs like stinging nettle leaf, butterbur extract, fisetin, and perilla futescens can modulate the immune system response to allergens and histamines. 

  • HistaQuel 2 pills 2 times a day. This product by Researched Nutritionals is a source of quercetin, luteolin, stinging nettle leaf, butterbur extract, fisetin, and perilla. 

When the above herbal options to stabilize mast cells are not effective enough or not tolerated, then I consider adding low dose naltrexone (LDN) or the KPV peptide, or both. Naltrexone works by binding to toll receptors on mast cells. This prevents infections and toxins from binding to these receptors and turning on the mast cells. KPV is also know to stabilize mast cells too. If you decide to add these agents, give the LDN at least 6 months for full effect. Give the KPV peptide at least 3 months to see if it will help. LDN requires a prescription from a compounding pharmacy. KPV is available as a supplement. 

  • LDN 1.5 to 4.5 mg 1 time a day taken in the morning. Start at 1.5 mg and increase every two weeks by 1.5 mg reaching 4.5 mg a day at 4 weeks. 
  • KPV 500 mcg 2 times a day. This comes as a spray or a pill. 

For more information see Low Dose Naltrexon (LDN) & Lyme and Key Oral Peptide Strategies to Repair and Restore in Lyme & Mold Toxicity.

Where to Start

Start with quercetin first, but in more difficult situations add luteolin or consider the HistaQuel. If these are not effective, then add in the LDN and the KPV. You can find products containing these key supplement ingredients on the Immune System aisle at Marty Ross MD Supplements. Note the luteolin I recommend is found in a product called Neuroprotek. 

Another option is to use the prescription cromolyn sodium, but this works best only for GI symptoms. And the nasal spray form works best for nasal allergies. The problem with the oral form, is it is very expensive.

8. Try a Low Histamine Diet

According to the Institute for Functional Medicine in its Elimination Diet Comprehensive Guide:

"In general, foods to avoid on a low-histamine diet include: bananas, chocolate, strawberries, tomatoes, egg whites, pork, sauerkraut, cheeses, fermented soy products, sausage, spinach, ketchup, eggplant, alcoholic beverages, smoked meats, vinegars, and canned fish, coffee and tea, leftover meats along with certain food additives and preservatives such as tartrazine and other food colors, benzoates, BHA, and BHT."


When it comes to supplements or prescriptions, start first with curcumin, quercetin and consider luteolin or HistaQuel. These tend to have no side effects and work well. If they do not work, then consider adding the antihistamines and leukotriene inhibitors plus the LDN and KPV. 

And I cannot stress strongly enough the importance in this disorder of finding ways to remove and deal with stress.


The ideas and recommendations on this website and in this article are for informational purposes only. For more information about this, see the sitewide Terms & Conditions.

* These statements have not been evaluated by the Food and Drug Administration. These products are not intended to diagnose, treat, cure, or prevent any disease.


View Citations

  1. Theoharides, T. (2016). Mast Cell Activation. Lecture presented at ILADS annual meeting, Philadelphia.
  2. Theoharides, T., Valent, P., Akin, C., Mast Cells, Mastocytosis, and Related Disorders. N Engl J Med,373;2, 163-172. (View)
  3. Talkington, J., & Nickell, S. P. (1999). Borrelia burgdorferi Spirochetes Induce Mast Cell  Activation and Cytokine Release. Infection and Immunity, 67(3), 1107–1115. (View)
  4. Institute for Functional Medicine. Elimination Diet Comprehensive Guide. Version 6. IFM 2016.
  5. Peptide Therapy Certification - Module I. Lectures presented at the Advanced Anti-Aging Medicine Conference; September 2022; Boston, MA.
  6. Peptide Therapy Certification - Module II. Lectures presented at the Advanced Anti-Aging Medicine Conference; December 2022; Las Vegas, NV.
  7. Weinstock L, Cottel J. Low Dose Naltrexone and Autoimmune Disease Therapy. Lecture presented at the Institute for Functional Medicine Annual International Conference; 2018; Hollywood FL.
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About The Author

Marty Ross, MD is a passionate Lyme disease educator and clinical expert. He helps Lyme sufferers and their physicians see what really works based on his review of the science and extensive real-world experience. Dr. Ross is licensed to practice medicine in Washington State (License: MD00033296) where he has treated thousands of Lyme disease patients in his Seattle practice.

Marty Ross, MD is a graduate of Indiana University School of Medicine and Georgetown University Family Medicine Residency. He is a member of the International Lyme and Associated Disease Society (ILADS), The Institute for Functional Medicine, and The American Academy of Anti-Aging Medicine (A4M).

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