I have recently returned from a most stimulating conference/think tank with Dr. Afrin and 30 other leading clinicians on Mast Cell Activation Syndrome (MCAS) at Commonweal—a cancer retreat centre in northern California.
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, 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. While we need mast cells to protect us from threats, 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
- Trouble with allergies 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 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 MCAS, I encourage you to read my article: Mast Cell Activation Syndrome and Histamine: When Your Immune System Runs Rampant.
The most common drugs that are prescribed for treating MCAS include:
- Histamine 1 blockers – Hydroxyzine (Atarax), Doxepin (Silenor), Cyproheptadine (Periactin), Loratadine (Claritin), Fexofenadine (Allegra), Diphenhydramine (Benadryl), Ketotifen (Zaditen) and Cetirizine (Zyrtec, Reactine).
- 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 drugs to help your symptoms, there are also several natural treatment options. A benefit of using natural treatments for MCAS 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, 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 Treatments 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 Treatments 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, 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.
1. Stabilising Mast Cells
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 mediators mast cells release and can be broken down into three groups (A, B, and C) based on how helpful and potent they are.
The “A” Team:
- Quercetin – 2000 mg daily, dose divided
- 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
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
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 (dihydrocodeine) – 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
- 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 allergies, 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.
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
- 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
- Found in grapes, berries and peanuts
- Reduces the expression of inflammatory markers IL-6 and IL-8
- Inhibits IgE allergy reactions
- 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
- 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
Other supplements that have been used in MCAS:
- Lipoic acid
- 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
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.
2. 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 and alcohol metabolic pathways share common enzymes—aldehyde oxidase and aldehyde dehydrogenase. When you drink alcohol, histamine is 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 activation.
3. Reducing Histamine Levels
To reduce histamine levels in your body, you should adopt a low histamine diet. Avoid the following:
- Smoked and cured meat
- Pickled foods
- Fermented foods
- Canned fish or meat
- Berries, especially strawberries
- Nightshades, including tomatoes and potatoes
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.
4. Stabilising the Immune System and Reducing Inflammation
Calming the immune system and reducing inflammation is a critical part of 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:
- Bifidobacterium adolescentis
- Bacteroides thetaiotaomicron
- Bacteroides fragilis
- Lactobacillus rhamnosus
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 or call 403-206-2333.
Dr. Bruce Hoffman, MSc, MBChB, FAARM, IFMCP is a Calgary-based Integrative and Functional medicine practitioner. He is the medical director at the Hoffman Centre for Integrative Medicine and The Brain Centre of Alberta specializing in complex medical conditions. 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.