MCAS is a type of mast cell activation disorder (MCAD) characterised by an abnormal activation of mast cells resulting in chronic multisystem polymorbidity of a general inflammatory nature, with or without an allergic nature. Mast cells are white blood cells that are concentrated at the entrances to body tissues (ears, nose, throat, skin, genitalia, rectum), and when activated, they release over 200 signalling chemicals (e.g. histamine, prostaglandins, leukotrienes, cytokines and chemokines). These chemical mediators trigger inflammation in response to the invasion of foreign toxins, infections or chemicals, resulting in a range of chronic symptoms. With MCAS, this function becomes upregulated and chronic, occurring at inappropriate times in response to substances that are not necessary a threat. This can lead to widespread symptoms in many different body organs and systems.
Mast cells are located throughout your body in many different tissues, primarily including dermatological, gastrointestinal, neurological and respiratory tissues. Usually, mast cells play to protect us from threats, but here they become a problem when they are overactive and hyper-responsive and will not ‘turn off’. Dr. Afrin, a leading mast cell researcher, believes that between 15 and 20% of the North American population may be affected by MCAS. The symptoms of MCAS vary greatly. As a result, many people spend years, even decades, in search of a correct diagnosis, visiting many different subspecialists. What is more frustrating for patients is that many doctors are not familiar with the multiple ways in which MCAS may manifest.
MCAS is often found in individuals with hypermobility syndromes (Ehlers–Danlos syndrome), postural orthostatic hypotension (POTS) as well as chronic inflammatory response syndrome (CIRS) and tick-borne illnesses (Lyme disease and co-infections).
The most common symptoms of MCAS include:
Feeling as though you have been sick forever
Allergic reactions and asthma
Overreaction to insect bites, bee stings and chemical intolerances
Facial and chest flushing
Skin rashes that come and go, including hives and angioedema
Itchiness and a burning feeling
Brain fog and headaches
Poor wound healing and easy bruising
Waxing and waning of symptoms
The condition may be mild in some people and only exacerbate in response to a significant life stressor, which may be either physical or psychological in nature (divorce, bankruptcy, loss of job, travel, infection, death of a loved one, exposure to novel infections, occupying a water damaged building, exposure to cold or heat).
In others, symptoms may develop from a young age and slowly become worse over time. People with MCAS are likely to experience a few of the most common symptoms. Because human mast cells are located throughout the body, symptoms can affect the eyes, nose, ears, throat, skin, heart, blood, lungs, gastrointestinal tract and the nervous, endocrine and musculoskeletal systems.
The symptoms of MCAS are often confusing. For a long time, many people with MCAS have been told that their condition was psychosomatic or ‘in their head’. Fortunately, awareness of this frustrating and debilitating condition is spreading. Testing for MCAS is somewhat complex and confusing, as positive biomarkers may only be observed when a patient has a flare up. Incorrect collection of specimens may also lead to false negative testing. Many specimens need to be chilled with a refrigerated centrifuge, which is not available in every lab or doctors’ office.
If you need a comprehensive overview of MCAS, I encourage you to read my article: Mast Cell Activation Syndrome and Histamine: When Your Immune System Runs Rampant. 12+ Mast Cell Stabilizers To Treat MCAS
The most common drugs that are prescribed for treating MCAS (not natural) include:
Histamine 2 blockers – Famotidine (Pepcid, Pepcid AC), Cimetidine (Tagamet, Tagamet HB) and Ranitidine (Zantac). Famotidine is chosen most often because it has fewer drug interactions than Tagamet.
Mast Cell Stabilisers – Cromolyn (Cromolyn Sodium, Gastrocom—oral form, Nasalcrom—nasal spray, Opticrom—eye drops, and there is a nebulised form and a cream can be made from a bottle of Nasalcrom and Eucerin or DMSO cream), Ketotifen (both a mast cell stabiliser and an H1 blocker) and Hydroxyurea (Hydrea).
Mast Cell Inhibitors – Montelukast (Singulair), Zafirlukast (Accolate) and Zileuton (Zyflo). Pentosan (Elmiron) is used in the genitourinary tract for perineal pain and interstitial cystitis.
Antibody neutralisers – Omalizumab (Xolair).
Tyrosine Kinase Inhibitor – Imatinib (Gleevac).
Stimulants – Mixed salts amphetamine (Adderall XR), Methylphenidate (Ritalin) and Ephedrine (Epipen provides an acute rescue injection when experiencing an anaphylactic episode).
Non-steroidal anti-inflammatory (NSAIDS) – Helpful in some, a trigger in others. Aspirin is the most commonly used NSAID. COX 2 selective NSAIDs—Celecoxib (Celebrex)—are also used.
Low-dose Naltrexone (LDN) – Used in a step-up dosing at night.
Cannabinoids – Drobaninol downregulates neurons and mast cells via inhibitory cell-surface cannabinoid receptors (not available in Canada). CBD is more helpful than THC.
Benzodiazepenes – Addresses the inhibitory mast cell benzodiazepine receptors. Use short-acting varieties. Lorazepam (Ativan) and Clonazepam (Klonopin, Rivotril) are best when used three times daily. Valium and Midazolam are also sometimes used.
Selective Serotonin Reuptake Inhibitors – may occasionally be of benefit.
IV Immune Globulin (IVIG) – this treatment is sometimes used in MCAS.
While your doctor may prescribe you some of these mast cell stabilizer drugs to help your symptoms, there are also several natural ways to stabilize mast cells. A benefit of using natural mast cell stabilizers is that you can take these on your own and they do not require a prescription. However, because most patients with MCAS present differently, it is a good idea to implement these with the guidance of a functional medical doctor who is experienced in MCAS.
Although there is a good possibility that you will eventually find the right therapeutic combination of treatments that will help alleviate many of your symptoms, the fact is that there are no specific biomarkers that will predict which therapy will be the most effective for your specific manifestation of this condition. Trial and error with both drug- and non-drug-based options is often the name of the game.
Also, if you opt for natural treatments for MCAS and mast cell activation disorder, always be sure to disclose everything you are taking to your doctor so he or she has a clear idea of what is going on. It is also important that you make only one change at a time when attempting different combinations of treatment options.
Advantages of Using Natural Stabilizers for Mast Cell Activation Syndrome
There are many advantages of using natural treatments for MCAS, including:
Lower cost
No need for a prescription
MCAS patients are often sensitive to pharmaceuticals, particularly the excipients (bulking agents, binders, fillers, dyes) within the products. Patients will have to work closely with their compounding pharmacists to help identify a list of offending ingredients in drug formulations. If a patient has a strange reaction to medications (e.g. insomnia while using a typically sedating antihistamine), it is likely a flare up of mast cells in the CNS causing the problem and not the drug itself.
Some drugs block DAO—an enzyme in the gut that breaks down histamine
Many patients prefer natural treatments
May have benefits beyond mast cell stabilisation
Disadvantages of Using Natural Stabilizers for Mast Cell Activation Syndrome
Supplements are bioactive compounds that may have unacceptable effects
They may interfere with known medications
They still have to be processed through the same liver detoxification enzymes as pharmaceuticals and thus may have unacceptable side effects
Supplements may also contain excipients that produce unacceptable side effects
Many of my patients find that these natural treatments are sufficient when it comes to treating their MCAS. For others, these natural treatments allow them to reduce the number or amount of drugs they need. When it comes to natural treatments for MCAS and mast cell activation disorder, the most effective work in the following ways:
Stabilising mast cells
Increasing histamine breakdown
Reducing histamine levels
Stabilising the immune system and reducing inflammation
With that in mind, here are some of the best natural treatments for MCAS according to the mechanisms they influence. These recommendations were presented at the think tank by Dr. Brian Bouch, a leading integrative medical doctor from California.
10 Natural Mast Cell Stabilizers To Treat MCAS
One of the best things you can do for MCAS is add natural treatments that stabilise your mast cells. Such therapies work by inhibiting the inflammatory mediator release and can be broken down into three groups (A, B, and C) based on how helpful and potent they are.
Green tea (EGCG, L-Theanine) – 2 to 3 cups daily. Supplement with 500 mg (175 mg of ECGC) twice daily
Curcumin (Meriva is a common brand name) – 1 to 4 g daily, dose divided
Chamomile tea (Apigenin, luteolin) – 1 to 2 cups before bed
Resveratrol – 20 mg twice daily
Diamine oxidase enzymes (DAO) – 2 capsules with each meal
Vitamin C – may need a non-citrus source such as rose hips – 1 to 3 g daily
2) The “B” Team
Luteolin – 100 mg twice daily
Ginkgo biloba – 500 mg daily
Silymarin – 500-1000 mg daily, doses divided
Shea oil – 3 capsules daily
Ellagic acid – 500 mg daily
Pycnogenol – 500 to 1000 mg daily
Magnolia/Honokiol – 200 to 250 mg twice daily
Parthenolide (Feverfew) – 200 to 400 mg twice daily
3) The “C” Team
Fiestin – 100 mg twice daily
Rutin – 200 mg daily
Genistein (isoflavone)
Mangostin (often taken as a juice) – 500 to 1000 mg daily
Xanthium (dihydroleucodeine, also known as cocklebur) – 6 to 9 capsules daily
Isatis (indoline) – 6 to 9 capsules daily
Here is some further information about select products that are used most often
4) Quercetin
Found naturally in stinging nettle, grapefruits, onions, apples, black tea, leafy green vegetables and beans
Downregulates the enzyme that converts the protein histidine to histamine—histidine decarboxylase
Inhibits the release of histamine, prostaglandins and leukotrienes— three of the most common inflammatory mediators found in MCAS
Decreases the production and release of inflammatory cytokines—the inflammatory mediators responsible for many of the symptoms of inflammation related to MCAS
Often used as a primary therapy—has been shown to be more effective than the pharmaceutical Cromolyn
Treats allergic reactions, contact dermatitis, photosensitivity and inflammation
The dihydrate form has the best bioavailability
Dr. Theoharides, a top mast cell researcher, has produced a product called NeuroProtek, which contains quercetin, luteolin and rutin. At least 8 capsules must be taken daily for maximum effect.
5) Green Tea – EGCG
EGCG is the most common polyphenol found in green tea
Inhibits calcium influx into mast cells, thus preventing their degranulation
Inhibits mast cell production of inflammatory mediator leukotriene C4.
Has other benefits: improves brain function, improves dental health, lowers risk for cardiovascular disease, combats skin aging
Lowers risk for Alzheimer’s disease, Parkinson’s disease and diabetes mellitus
6) Curcumin
Widely used in popular supplements for lowering inflammation
Best found in phospholipid forms such as Meriva
Has antiallergic activity—inhibits the degranulation of mast cells in a dose-dependent manner
Inhibits inflammatory molecules—interleukin-4 and tumour necrosis factor -?
Widely used in cancer and joint inflammation
7) Resveratrol
Found in grapes, berries and peanuts
Reduces the expression of inflammatory markers IL-6 and IL-8
Inhibits IgE allergy reactions
8) Vitamin C
Research has shown that when Vitamin C levels fall in the blood, histamine levels increase exponentially. When Vitamin C is reintroduced, histamine levels fall exponentially
There is very little evidence in the literature, however, to support its use as a natural antihistamine
It is frequently combined with quercetin in supplements—a popular supplement is Natural D-Hist by Ortho Molecular Products. Take 2 three times per day for maximum effect
Be careful of citrus-based Vitamin C and be aware that high does can cause diarrhoea. It is best to take smaller amounts more frequently
Slow-release formulations may be better
9) Silymarin
Silymarin, an extract of milk thistle, which has been shown to attenuate mast cell-mediated anaphylaxis-like reactions
It also prevents the release of proinflammatory cytokines such as tumour necrosis factor, interleukin 6 and nuclear factor–kappa B.
Also known to have hepatoprotective, anti-carcinogenic and anti-inflammatory effects. Widely used to protect against drug- and chemo-induced liver toxicity
10) Other supplements that have been used in MCAS
Lipoic acid
N-acetylcysteine
Ashwagandha – an Ayurvedic remedy known as an adaptogenic herb that modulates the body’s response to stress. Withaferin A is a compound found in ashwagandha that has been shown to prevent mast cells from releasing histamine and other inflammatory mediators
Vitamin D – usually best at higher doses. Need to test blood levels
Top Tips For Stabilizing Mast Cells (Important Caveats)
Both quercetin and green tea extracts may inhibit the COMT enzyme. If you have a COMT ++ enzyme (slow function) on your 23andme, be careful when using these two supplements. The COMT gene determines your ability to process catechols, oestrogen and the major neurotransmitters adrenaline, noradrenaline and dopamine. Your anxiety, insomnia and pain may increase due to further slowing down of the excretion of these excitatory chemicals plus the excitatory catechols, substances found in green and black tea, coffee, chocolate, green coffee-bean extracts and quercetin.
Other things to consider in MCAS patients:
Ensure you have sufficient magnesium levels, as a deficiency has been shown to induce the emergence of mast cells, particularly in the liver. Magnesium also has hundreds of other important functions in a healthy body.
Zinc is another mineral you should ensure you’re getting enough of because it is important in appropriate mast cell signalling.
Stress reduction is also important in stabilising mast cells. When you’re stressed, your body releases corticotropin-releasing hormone (CRH), which is associated with the activation of skin mast cells. Incorporate meditation, yoga, breathing exercises and other stress-reducing techniques into your daily life.
Maintaining a schedule is a great way to help stabilise your mast cells because they exhibit circadian rhythm patterns. Try to wake up and go to sleep at the same time each day. Also, avoid electronic screens before bed or wear a pair of blue-blocking glasses for better hormone regulation.
Increasing Histamine Breakdown
Diamine oxidase (DAO) stabilises mast cells, but more importantly, it is the predominant enzyme that breaks down histamine. To increase your DAO levels, you can take DAO enzymes. I recommend taking two capsules with each meal. You can also increase your DAO levels with high doses of vitamin C.
You should also avoid anything that blocks the release of DAO. First and foremost, this includes any form of alcohol. Histamine release and alcohol metabolic pathways share common enzymes—aldehyde oxidase and aldehyde dehydrogenase. When you drink alcohol, histamine released from your mast cells and DAO is simultaneously inhibited. This can cause a runaway chain reaction, which results in greater sensitivity to alcohol and worsening histamine intolerance. Aged cheese and wine together may induce a major mast cell function and activation.
Reducing Histamine Levels
To reduce histamine release in your body, you should adopt a low histamine diet. Avoid the following:
Alcohol
Smoked and cured meat
Seafood
Pickled foods
Fermented foods
Leftovers
Canned fish or meat
Berries, especially strawberries
Nightshades, including tomatoes and potatoes
Preservatives
Vinegar
Try to eat foods as fresh as possible, and stick to anti-inflammatory foods. Adding rosemary oil to fish reduces histamine formation as the fish ages.
For a comprehensive resource on low-histamine foods, diets and recipes, I recommend my guide on the Low Histamine Diet as well as Healing Histamine.
Stabilising the Immune System and Reducing Inflammation
Calming the immune system and reducing inflammation play a critical role in any MCAS protocol. The recommendations above mainly help to stabilise the immune system and reduce inflammation, though there are a few other effective methods:
Check and treat any underlying infections – These can contribute to a widespread inflammatory response in the body if left untreated. These may include H. pylori, Epstein Barr and herpes simplex.
Correct gut dysbiosis – Correcting the balance of your gut microbiome has been shown to reduce inflammation and improve immune system health. Specifically, there are certain strains of probiotics that have been shown to help breakdown histamine, including:
Many patients will need to experiment with various therapeutic options at different doses until they find the right combination of medications that helps with their particular symptoms. If unusual side effects are experienced with known medications, remember that the excipients contained within the medications may be the problem, not the medications themselves.
While there is no cure for MCAS, there is a lot you can do to minimise the condition’s impact on your life. The good news is that most of the natural treatments for MCAS are recommendations for a healthier life that anyone would benefit from. To read more about living with MCAS, check out 12 Tips for Living With Mast Cell Activation Syndrome
With a chronic illness such as MCAS, it is possible to live a full life—the treatment just requires a careful, comprehensive approach. If you believe you have MCAS or have already received a diagnosis and need a functional medical doctor who specialises in MCAS in Calgary, Alberta, you can request an appointment here call 403-206-2333.
Dr. Bruce Hoffman, MSc, MBChB, FAARM, IFMCP is a Calgary-based Integrative and Functional medicine practitioner. He is an integrative medicine educator and creator of the Seven Stages to Health & Transformation program.
He was born in South Africa and obtained his medical degree from the University of Cape Town. He is a certified Functional Medicine Practitioner (IFM), is board certified with a fellowship in anti-aging (hormones) and regenerative medicine (A4M), a certified Shoemaker Mold Treatment Protocol Practitioner (CIRS) and ILADS trained in the treatment of Lyme disease and co-infections.
He is the co-author of a recent paper published by Dr. Afrin’s group: Diagnosis of mast cell activation syndrome: a global “consensus-2”. Read more about Dr. Bruce Hoffman.
