Mast Cell Activation Syndrome (MCAS)

The Growing Epidemic of Chronic Inflammatory Disease

Chronic inflammatory diseases are on the rise. It is estimated that 30% of the population is now affected by an inflammatory condition expected to rise to 50% by 2030.

Many chronic inflammatory diseases (CID)’s can be attributed to poor, poor food choices, obesity,  toxins in the environment, and chronic stress. However, there is an emerging theory that some of the epidemic amounts of CID can be explained by “Histamine Intolerance”  (HIT) or Mast Cell Activation Syndrome”  (MCAS). Histamine is one of the most important symptom causing mast cell chemicals.

Histamine intolerance occurs when the body has an overabundance of histamine due to the inability to break it down. This would be similar to lactose intolerance, when the body lacks the enzymes necessary to break down lactose. This typically occurs from eating too many foods high in histamines such as fermented foods, citrus, wine, beer, or hard cheese  and from the inability to break down histamine from genetic mutations in either of two pathways, HNMT and DAO.

If one of these pathways cannot break down histamine due to genetic mutations or a deficiency of essential nutrients, histamine will build up and cause various symptoms in the body.

MCAS or Mast Cell Activation Syndrome (MCAS) differs from histamine intolerance. It occurs when the mast cells, which are part of the immune system, release histamine due to being over-reactive. This over-reactivity causes an inappropriate and excessive release of a variety of chemical mediators, including histamine, interleukins, and prostaglandins, causing inflammation.  In other words, mast cells go haywire, resulting in a range of chronic symptoms that is highly unique to each individual and confounds most doctors.  No system in the body is immune to MCAS.  Having MCAS can exacerbate and complicate other diseases.  MCAS is becoming more known in the medical world, but it is still far from mainstream.

What are MCAS triggers?

MCAS triggers can be any of the following: Viruses, bacteria, mold, drugs or drug excipients, parasites, sun, stress, venoms, vibration, chemicals, nutritional deficiencies, hypoxia, hormone imbalances, pollen, allergies, vaccines, heavy metals, insect bites, parasites, foods, pesticides, hot or cold.

MCAS  could be a much bigger problem than we know. According to Lawrence Afrin, one of the foremost experts on MCAS in the world. In 2016, it was believed that as many as 14-17% of the general population was affected. By the time most people have been diagnosed, most MCAS patients have been chronically ill for decades.  One of the reasons it has been hard to diagnose is that there is no uniform clinical presentation and the degree of severity is very individual. Also, testing for histamine and other inflammatory mediators is challenging because of the rapid degradation of these chemicals resulting in many false negatives.

How is Histamine Intolerance or MCAS diagnosed? 

1. Having fluctuating episodes of signs and symptoms consistent with MCAS in at least 2 body systems and a doctor that can recognize the symptoms.

2.  A response to therapy from taking mast cell stabilizers, anti-histamines such as Zertec or Pepcid or a low histamine diet. May require trials of different anti-histamine medications or supplements.

3.  Lab tests showing an increase in serum or urine markers indicating mast cell activation. Lab tests to diagnose MCAS are a challenge and often show false negatives. Plasma histamine,  tryptase, Chromogranin A, 24-hour urine test for N methyl histamine or PGD2,. Factor VIII, TNF alpha, and IL-6 can also be elevated. A better bet might be to do a  pre and post-MMP9 blood test after challenging with low histamine or high histamine foods for 2 weeks.

4.  Due to the high cost of testing and test unreliability,  a low histamine diet trial is often the best way to diagnose MCAS.

COMMON MCAS SYMPTOMS:   fatigue, fibromyalgia, headaches, itching, swollen lymph nodes, nausea or vomiting, unusual skin sensations, rashes, eye irritation, shortness of breath, brain fog, gut pain, memory issues, insomnia, dizziness/lightheadedness, environmental allergies, mouth sores, anxiety, heat or cold intolerance, diarrhea, constipation. The trouble with skin, hair, nails, and teeth is common.

A More Complete List of Symptoms and Disorders:

Neurological: vertigo, dizziness, POTS, neuropathy, chronic headaches, migraines, resting tremors, tics and seizure disorders

GUT: Migratory pain in the intestines, Irritable Bowel Syndrome, nausea, vomiting, diarrhea, acid reflux

Kidney/Bladder: cystitis, urethritis, prostatitis, erectile dysfunction, flank pain or low back pain,

Female: endometriosis, vaginitis, decreased libido

Muscles/Bones: fibromyalgia, arthritis, joint hyper mobility, Pain not responsive to pain medication, osteoporosis/osteopenia

Psychiatric: Anxiety, depression, bipolar, ADHD, PTSD, panic attacks, memory problems, brain fog, sleep problems

Endocrine: Abnormal electrolytes particularly magnesium, painful periods, hypothyroid, hyperthyroid, weight changes, increased liver enzymes

Blood: Anemia, easy bruising, blood clots, elevated eosinophils or monocytes

Immunology: Hypersensitivity reactions, autoimmunity, impaired healing, increased susceptibility to infection, elevated or decreased immunoglobulins

Constitutional: Fatigue, or chronic fatigue syndrome, feeling cold, sweats, flushing, itching, environmental sensitivities, appetite changes, low level fever, anaphylaxis.

Skin: Rashes, warts, tags, ulcers, striae, dermatographism, hair loss, swelling, flushing, itching, hives.

Eyes: irritated, red, dry, conjunctivitis, sun sensitivity, difficulty focusing

Ears: tinnitus, hearing loss, sound sensitivity

Oral: Burning mouth, mouth ulcers, dental decay, post nasal drip, throat tickle

Lymph: enlarged lymph nodes (often changeable), enlarged spleen

Nose/Lungs: Chronic runny nose, sinusitis, laryngitis, bronchitis, cough, shortness of breath, wheezing, sleep apnea

Heart: Lightheadedness, weakness, dizziness, fast heart rate, vertigo, high and low blood pressure, varicose veins, palpitations, arrhythmias, chest pain, migratory edema.

Mast Cell Dysregulation Can Now be Considered Possible Causes of the Following Disorders:

Brain Fog: Hypersensitive mast cells in the brain trigger microglial cells, which produce inflammatory chemicals, causing brain fog and cognitive dysfunction.

Adrenal Dysregulation: When the body has been in stress response for too long, the adrenal glands can stop making cortisol, causing adrenal insufficiency. This can cause mast cell activation. Mast cell activation can activate the HPA axis or not, but it usually activates it. The inflammation created by mast cells can turn on the HPA axis, activating mast cells even more. This means that if you have frequent mast cell activation, your body can end up in a constant fight or flight response.

Insomnia or Somnolence (excess sleepiness): Improper or insufficient synthesis of histamine can lead to somnolence, while excess histamine can lead to insomnia.

Irritable Bowel Syndrome due to Small Intestinal Bacterial Overgrowth: A 2016 study on the low FODMAP diet for IBS patients demonstrated not only an improvement in digestive symptoms but an eightfold reduction in histamine levels in the low FODMAP group.

Obesity - Now recognized as a chronic systemic inflammatory condition, and MCAS is believed to be one of many causes. Prostaglandin D2 (one of the inflammatory mediators released from mast cells) has been associated with obesity.

Diabetes Mellitis Type 2 -  Now recognized as a chronic inflammatory disease with one cause being MC disorders. In both experimental animals and humans, Mast cell stabilizers were able to prevent DM2 and delay the onset of Diabetes 1 in experimental animals.

Metabolic Syndrome - A syndrome of impaired glucose tolerance or type 2 diabetes with two or more abdominal obesity, hypertension, high triglycerides, and or low levels of high-density lipoprotein cholesterol. Because Mast cells are involved in the specific disorders that compose metabolic syndrome, it is believed that they may also cause Metabolic Syndrome.

Asthma - Large numbers of Mast cells are found in the respiratory tracts of asthmatics.

Progesterone is a mast cell inhibitor, and estrogen drives mast cell degranulation. It is believed that when asthma worsens just before menses, it is due to the low progesterone driving the increase in histamine release that causes asthma attacks to flare.

Fibromyalgia -Increased numbers of activated mast cells have been repeatedly found in random skin biopsies of fibromyalgia patients. Inflammatory chemicals released from mast cells such as IL-1, IL-6, and TNF-alpha have also been found in the skin of FM patients.

Autism Spectrum Disorder (ASD) - With ASD is now being considered an epidemic, with 1 in 45 children in the US diagnosed with ASD. It is conceivable that MC activation may contribute to ASD where vaccinations, an immune stressor given in early childhood, create a systemic reaction constant with MC activation. It is believed certain genetic variants predispose children to allergic-type reactivity risks from certain vaccines.

Attention deficit Hyperactivity Disorder - Many allergic reactions from foods, preservatives, and dyes lead to mast cell degranulation, and it is known that these allergies can contribute to ADHD. Many pro-inflammatory mediators have also been found in those with ADHD, consistent with those released from mast cells. The inflammatory mediators may pass the blood-brain barriers and affect behavior and emotions.

Depression -Depression has both been shown to have a component of central nervous system inflammation, and the source of the inflammation remains unclear. Experimentally induced allergy to tree pollen ha bee reported inducing depressive-like behavior and mast cell activation in the brain of female rats. Some antidepressants have been found to partly have anti-inflammatory effects by inhibiting mast cell degranulation.

Autoimmunity - Mast cells are initiating and activating a wide range of autoantibodies and autoimmunity, such as autoimmune thyroiditis (Hashimotos)

Bipolar - Bipolar disease is recognized as having a neuroinflammatory factor in which the cause is unclear. It is theorized that BP may be a multi-system inflammatory disorder involving the innate immune system as many pro-inflammatory mediators have been found in which mast cells are a known source. Systemic MC activation has been seen in Bipolar.

And more…Chronic kidney disease, migraine headaches, endometriosis, polycystic ovarian syndrome, restless leg syndrome, burning mouth syndrome, dysautonomia, Gulf war syndrome.


Dr.’s Afrin and Theorides, the leading experts on MCAS say there is no global consensus on how to treat this disorder.

1. Identification and avoidance of triggers is foremost. Refer back to triggers of MCAS.

2. Following a low histamine diet and or diet for SIBO (small intestinal bacterial overgrowth). Histamine is also a degradation product of proteins so protein leftovers must be avoided when possible.

3.  Using either natural or pharmaceutical antihistamines. H1 and H2 blockers may be used as well as aspirin, NSAIDs and leukotriene inhibitors such as Singulair. Histamine blockers temporarily block the histamine receptor suppressing the effects histamine would have on a particular cell but do not reduce the amount of histamine in the body.   H1 receptor blockers have the greatest therapeutic benefit.  A “trial and error” approach is required due to the individual variation between patients.  Whenever possible, one intervention should be tried at a time, generally starting at a low dose and escalating step-wise in dose or frequency about every 1-2 weeks as tolerated so that a maximally tolerated dose and a maximally effective dose and frequency can be clearly identified. If the intervention is tolerated, but the significant benefit is not clearly identified after 4-8 weeks, the drug should be dropped, and the patient should proceed to the next trial.

4. Mast cell stabilizing agents do not block receptors but stabilize the mast cell to reduce its overactivity. Mast cell stabilizers include  ketotifen, vitamin D or quercitin.

5.  Genetic SNPs. I like to check the patient’s genetics, and if finding SNPs(mutations) in their histamine genes, it often clues me into how to support that gene with various nutrients. There are numerous pathways responsible for metabolizing histamine.

6. Using co-factors to support the pathways that degrade histamine include Vitamins C, B6, B12, Magnesium, Folate, and B-1. Copper. To be safe, I recommend that people start with the ones less likely to cause reactions, such as Magnesium, Vitamin C, B6, and hydroxy B12.

7. Exercise is encouraged but often low, intensity exercise such as yoga or walking is better tolerated.

8. Stress reduction of any kind is very important.

9.  Small Intestinal Bacterial Overgrowth (SIBO) treatment if present as pathogenic bacteria in the gut, releases histamine.

10. When using probiotics, use Lactobacillus Rhamnosus. Avoid Lactobacillus Casei and Bulgaricus, both known to raise histamine

What Can You do If You suspect MCAS? 

Try a low histamine diet and stay away from leftovers, and include histamine support such as Histamine Scavenger, Luteolin, and DAO enzyme before meals. Do your best to stay away from histamine triggers such as stress, mold exposure, toxins, and unnecessary immunizations, and get enough vitamin C and  D (vitamin D is needed to keep the mast cells stable).

The bottom line is that  Mast Cell Activation Syndrome mimics other well-known disorders, so if you haven’t gotten anywhere with your current treatment and have many of the symptoms, consider MCAS as a possible cause of your inflammatory health condition.

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