Mast Cell Activation Syndrome, Postural Orthostatic Tachycardia Syndrome, and Ehlers-Danlos Syndrome: What is the Connection

Imagine it: you are a 35 year old female. You used to love to go to the gym, but have been diagnosed with Ehlers-Danlos Syndrome, and now you’re lucky if you can walk down the stairs without pain and open the car door without your shoulder, ankle, knee, hip, shoulder, or wrist cracking and possibly even dislocating. Usually, you’re so fatigued you can barely get through lunch, but on a good day, when you’re less tired than usual and you try to go to the gym, you get so dizzy when you’re trying to do your body weight squats, you usually can’t even finish the workout you had planned. What is the world is wrong with you and why can’t anyone help you figure it out?! The good news is recent studies are showing a connection between this disease trifecta, Mast Cell Activation Syndrome (MCAS), Postural Orthostatic Tachycardia Syndrome (POTS), and Ehlers-Danlos Syndrome (EDS). While there is no cure, it can be very manageable if you know how to figure out your underlying triggers. This is where I hope I come in! As someone with this syndrome combo, I not only can offer you a research/medical perspective, but I can also offer you my own personal journey and how to successfully navigate yours.

Mast Cell Activation Syndrome: What Is It and What Are The Symptoms?

Mast Cell Activation Syndrome (MCAS), otherwise known as Mast Cell Activation Disorder (MCAD), is an immunological condition in which mast cells release excessive amounts of chemical mediators, which can result in a myriad of physical symptoms. Remember that mast cells are a necessary part of the immune system – they are the “heros” that activate the immune system when the body perceives a foreign invader. They are present throughout your entire body, especially in areas where your body is likely to come into contact with material from the outside, like your skin, digestive, and respiratory systems. The problem is when these same mast cell cells perceive many different things as a threat. Normal everyday things can be triggers, like medications, foods, supplements, physical and/or emotional stress, very cold or very warm temperatures, pressure, noxious odors, exercise/exertion, chemicals, bug bites, trauma, or other environmental toxins/biotoxins, like mold. I had an unfortunate run-in with some black mold last year that had me laid up for nearly 6 months. Now that I know how bad of a trigger it is for me, I need to avoid it at all costs!

Mast Cell Symptoms

How Do You Manage MCAS?

Managing your MCAS really depends on how severe your initial symptoms are. Sometimes trying a low histamine diet, like the one found in the 4-Phase Histamine Reset Plan, can be helpful in getting your symptoms under control, and as you feel better, you may be able to start adding foods back in. Sometimes people like to supplement their diets with a mast cell stabilizer. Natural options include foods with ascorbic acid, quercetin, B vitamins, and omega-3 fatty acids. For this, I recommend HistoRelief, which will provide you with a synergistic blend of nutrients that provides natural support to help balance the immune response by allowing you to naturally stabilize your mast cells and also eat foods that you enjoy without a significant reaction. If you’re finding that you can only tolerate a handful of foods without a reaction, you may need to try some medication first in order to get your symptoms under control before you can really start figuring out what to avoid. Remember that histamine, one of the more common chemical mediators released by mast cells, binds to different receptors throughout the body. The medications that may be necessary are H1 (zyrtec, claritin etc.) and H2 (ie. pepcid AC, zantac) blockers, which mostly act on vessels in the brain to dampen your reaction to histamine. Although these medications can be a necessary first start for extreme cases, they reduce the enzyme (DAO enzyme) responsible for breaking down histamine in the body. I would not recommend using these without guidance from a mast cell specialist.

Postural Orthostatic Tachycardia Syndrome (POTS)

POTS is a condition caused by too little blood returning to the heart when moving from a lying down to a standing up position (orthostatic intolerance) with a rapid increase in heart rate (tachycardia). People with POTS usually have low blood volume and high levels of norepinephrine (a neurotransmitter released during stressful situations), indicating increased sympathetic nervous system activation. Other reported symptoms in people with POTS include:

Blurred vision
Lightheadedness, dizziness, and/or fainting
Heart palpitations
Headaches
Difficulty concentrating
Fatigue
GI symptoms, such as nausea, cramps, bloating, constipation, diarrhea
Shortness of breath
Head, neck, or chest discomfort
Feelings of weakness
Sleep disorders
Exercise intolerance
Anxiety
Cold or painful extremities

Unfortunately, the cause of POTS is not well understood. Episodes typically begin after major surgery, trauma, or a viral infection; in women, symptoms may be noticed after pregnancy or may worsen right before menstruation. The good news is most cases of POTS are very manageable and typically have a good prognosis with appropriate management. Given the variety of reasons someone may be diagnosed with POTS, there is no single treatment that is going to work for everyone. The purpose of pharmacological treatment is to improve low blood pressure and issues with the heart and vessels that may be contributing to symptoms. Lifestyle changes, like drinking more fluids, exercising, and avoiding triggers, may be all that is necessary for management. I had difficulty exercising with my POTS: I would try to go down into a squat or a lunge and immediately, I would get dizzy even though I’ve worked out for years. If this is the case for you as well, trust me, you are not alone. Please stay tuned for my next blog post for more details on Exercise Intolerance!

POTS

MCAS and Its Relationship to POTS

New research is suggesting significant overlap between Mast Cell Activation Syndrome and disorders of the autonomic nervous system (the nervous system that you have no control over and includes things like your heart rate and breathing). MCAS should be taken into consideration in patients with POTS when the rapid increase in heart rate upon standing is also associated with intermittent flushing. Prolonged standing in patients with both MCAS and POTS may also cause the associated flushing, as well as shortness of breath, headache, lightheadedness, diarrhea, nausea, vomiting, and excessive urination. MCAS is also likely if a urine sample produced within 4 hours of a flushing episode reveals abnormally high levels of methylhistamine.

Ehlers-Danlos Syndrome (EDS)

Ehlers-Danlos Syndromes are a group of disorders that affect the connective tissues of the body, including the skin, bones, blood vessels, and other organs and tissues, caused by various genetic defects in the structure, production, and/or processing of collagen and the extracellular matrix, which is a network of carbohydrates and proteins that support the structural integrity of the cell. Collagen is the major component of most of the body’s connective tissue and provides both the strength and flexibility for us to move, bend, and stretch without anything breaking or tearing. Mutations in these genes, as seen with EDS, will result in poor collagen strength or a collagen deficiency in our tissues. There are 13 different subtypes of EDS, which are named based on the area affected. While it is outside of the scope of this article to go into each individual type, there is some overlap in the common signs and symptoms. If you think you have this disorder, the best way to determine which genetic variant you have is to undergo genetic testing to confirm an EDS diagnosis. The most common types of EDS are the hypermobility (EDS-HT), otherwise known as EDS-III, and classical subsets. The hypermobile type affects as many as 1 in 5,000 to 20,000 people, while the classical type occurs in about 1 in 20,000 to 40,000 people. All other forms of Ehlers-Danlos syndrome are very rare.

EDS is a complex and multisystem disease process that will look different depending on what type of collagen is altered. The more common types of EDS affect the skin and joints and are relatively benign, but can range up to life-threatening issues with some of the rarer types. Remember not everyone with EDS will have all of these symptoms!

The most common EDS symptoms include:

Joints: hypermobility (unusually large ranges of motion); increased incidence of joint dislocation; chronic joint pain
Skin: very stretchy, fragile, increased bruising, “spider veins,” abnormal scarring and wound healing
Bone: presence of osteoporosis, scoliosis from a young age
Gastrointestinal: presence of hiatal hernias, downward displacement of internal organs in abdominal region (visceroptosis), changes in gut movement
Eyes: small corneas, fragility
Heart: arteries with tendencies to rupture, valve issues

EDS

MCAS and Its Relationship to EDS

So it makes sense that MCAS and EDS would be related simply because mast cells are found in connective tissues throughout the body: you can’t have one without the other. When mast cells are activated, they release a variety of chemical mediators, like histamine, proteases, cytokines, and growth factors, to name a few. These compounds will cause swelling and inflammation in the surrounding tissues, which is appropriate when there is an actual threat or foreign invader. However, when mast cells are overactive, they release an overabundance of these mediators, resulting in MCAS. Mast cells tend to adhere to proteins in the extracellular matrix called fibronectin and vitronectin; this pairing can result in an increased production and release of cytokines, one of the types of proinflammatory chemical mediators released by mast cells. It is possible that the gene defects that result in collagen mutations may also contribute to abnormal mast cell functioning.

AND FINALLY: How are Mast Cell Activation Syndrome, Postural Orthostatic Tachycardia Syndrome and Ehlers-Danlos Syndrome Connected?

Researchers have discovered a subpopulation of patients with EDS-HT (hypermobility subset) and POTS that also have been diagnosed with MCAS. Patients with EDS-HT and POTS also seemed to exhibit symptoms consistent with those you would typically find in someone with MCAS. However, the relationship between the three does remain somewhat murky. Some experts think EDS causes POTS. And others will tell you that MCAS causes both POTS and EDS. A recent study, led by Joshua Milner at the National Institute of Allergy and Infectious Diseases, took 96 people with EDS-HT and mast cell issues. POTS symptoms were also prevalent. All study participants had higher than expected tryptase in their blood. Tryptase is a protein and well-known mast cell mediator that is an integral part of an immune system reaction and may be related to many of the symptoms seen in patients with EDS-HT and POTS. Usually, people with mast cell problems have normal levels of tryptase. With further tests, Milner discovered a subset of patients that had an extra copy of the gene that codes for tryptase, TPSAB1. Two genes equals double the amount of tryptase protein. Going back through the DNA records, it appeared that people who had high tryptase levels also had the TPSAB1 gene mutation and were all living with symptoms that were very similar to those described when talking about EDS-HT, POTS, and MCAS. The interesting thing is about 30% of people don’t make tryptase at all, so maybe it’s not necessary? Maybe a potential treatment method for this disease trifecta is figuring out how to shut down the production of tryptase?

Recommendations for MCAS, POTS, and EDS

Here is what I recommend for improving the trifecta of MCAS, POTS, and EDS:

Reduce Your Mast Cell Triggers

EMF is not the only thing that can trigger your mast cells. There are many factors that may trigger mast cell activation. Most mast cell triggers tend to come from your environment. Common triggers of MCAS include mold, allergens, chemicals, toxins, heavy metals, viruses, and stress. Reducing your mast cell triggers may help to reduce your symptoms of mast cell activation and histamine intolerance.

Eat an Anti-Inflammatory, Low-Histamine Diet

Histamine intolerance is a common consequence of MCAS. Following a high-histamine diet may further trigger histamine intolerance. I recommend following a low-histamine diet for at least several months until your symptoms improve.

Remove inflammatory foods from your diet, including refined sugar and carbs, refined oil, artificial ingredients, additives, deep-fried foods, sugary drinks, junk food, and overly processed foods. Follow a nutrient-dense diet rich in greens, vegetables, herbs, sprouts, organic grass-fed meat, organic, pasture-raised eggs and poultry, and fresh wild-caught fish. Choose organic whenever available.

Remove high-histamine foods and foods that can increase your histamine load. High-histamine foods that you should avoid include age cheese (e.g., goat cheese), citrus fruits, canned and cured meat (e.g., pepperoni, salami, bacon, lunch meat, hot dogs, and canned meat), dried fruits (e.g., apricots, dates, raisins, figs, and prunes), fermented foods (e.g., kefir, sauerkraut, soy sauce, and vinegar), fermented alcohol (e.g., beer, wine, and champagne), legumes (e.g., beans, lentils, soy, and peanut), certain nuts (e.g., cashew and walnuts), soured foods (e.g., buttermilk, sour milk, sour cream), smoked fish and certain types of fish (e.g., mackerel, mahi-mahi, anchovies, sardines, tuna, and fish sauce), certain vegetables (e.g., avocados, tomatoes, eggplant, and spinach), vinegar-containing foods (e.g., pickles and olives), and all overly processed foods because of the high histamine load from preservatives.

Avoid histamine-liberating foods that are low in histamine but trigger histamine release in your body, including alcohol, nuts, bananas, papaya, pineapple, strawberries, tomatoes, chocolates, wheat germ, cow’s milk, shellfish, and many artificial preservatives and dyes. Avoid DAO enzyme-blocking foods and drinks, such as alcohol, black tea, green tea, mate tea, and energy drinks.

Choose low-histamine foods, including organic animal protein, most greens, vegetables, and fresh fruits (except as listed earlier), and healthy fats, such as coconut oil, grass-fed butter, ghee, and organic extra-virgin olive oil. Try new recipes. I recommend all the low-histamine recipes in The 4-Phase Histamine Reset Plan: Getting to the Root of Migraines, Eczema, Vertigo, Allergies and More and my recipe books, Fifty One Low Histamine Air Fryer Recipes and Low Histamine Cooking in Your Instant Pot. My book also has a detailed list of low- and high-histamine foods you can and cannot eat. I also recommend that you follow my Histamine Reset Plan outlined in my Histamine Online Program.

Try Some Mast Cell-Stabilizing and Histamine-Reducing Foods and Supplements

You can boost the benefits of your anti-inflammatory, low-histamine diet by adding some foods that may help to reduce your levels of histamine and stabilize your mast cells. Quercetin helps to reduce histamine. Add quercetin-rich foods to your diet, such as grapes, apples, cranberries, black plums, cherries, black currants, chokeberries, blueberries, olive oil, cruciferous vegetables, kale, romaine lettuce, chicory greens, red leaf lettuce, cabbage, sprouts, asparagus, snap peas, peppers, and red onion. You may also try a quercetin supplement.

I also recommend adding foods that can help to stabilize your mast cells, including onion, peaches, nettle, apples, chamomile, moringa, watercress, Thai ginger, and fiber-rich foods. You may also try a DAO enzyme supplement to support histamine breakdown and HistoRelief.

HistoRelief is a synergistic blend of nutrients that provides natural support to balance your immune response. This blend features Tinofend®, a patented and clinically researched extract derived from the plant Tinospora cordifolia, which has a powerful ability to support immune regulation and immune response. As a result, it boosts your body’s ability to fight interstitial cystitis symptoms. It includes quercetin, nettle leaf, vitamin C, and bicarbonate salt to help inhibit histamine release, supports normal histamine metabolism, and improves immune health.

Improve Your Gut Health

Your gut microbiome health is closely connected to mast cell activation and histamine intolerance. Gut health issues, including leaky gut syndrome, small intestinal bacterial overgrowth (SIBO), candida, and other gut infections are common underlying issues in mast cell activation and histamine intolerance. EMF exposure may also increase gut microbiome imbalance and gut infections.

Addressing any gut health issues and improving gut microbiome imbalance may help to improve your chronic symptoms and help to regain your health. Along with a gut-friendly anti-inflammatory diet, I recommend that you take a high-quality probiotics supplement to support your gut microbiome balance. For further gut-supporting supplements and a specific gut-health protocol, I recommend working with a functional medicine practitioner, like us.

Reduce Your Histamine Bucket

If you are dealing with symptoms of histamine intolerance, reducing high-histamine foods is not enough. High stress, poor sleep, not moving your body, and high toxin exposure may add to your toxin load. Stress and toxins may also cause mast cell activation. Improving these areas of your lifestyle may help to reduce your histamine bucket and lower the risk of mast cell activation.

Reduce Your Stress Levels

Chronic stress can increase mast cell activation and histamine intolerance. To decrease your stress levels, I recommend practicing breathwork, meditation, positive affirmation, journaling, yoga, grounding, and time in nature for stress and anxiety reduction. Taking an Epsom salt bath is another great way to relax your muscles, calm your mind, and detoxify your body.

Get Enough Sleep Sleep

Inadequate and poor sleep is another major underlying issue behind histamine intolerance. Chronic EMF exposure may also increase sleep issues and fatigue. Improving your sleep is absolutely essential for your health. Your goal should be to sleep at least 7 to 9 hours a night. Lower your stress levels throughout the day but especially in the evening time to support sleep. Take a bath, read a good book, listen to some music, journal, try coloring, and spend time with your family. Avoid sugar, alcohol, and heavy food in the evening. Sleep on a supportive mattress with comfortable and supportive pillows and blankets, and quality, organic cotton sheets.

Move Your Body

A lack of movement may also increase the risk of histamine intolerance and chronic health issues. Moving your body is a great way to reduce stress, improve detoxification, and improve your overall health. Move your body throughout the day. Stretch regularly. Take a stroll in the nearby park. Find creative ways to incorporate movement, such as an impromptu dance session, learning a new TikTok dance, playing with your kids or pets, taking the stairs, trying a treadmill desk, or practicing chair yoga. Exercise at least 20 to 30 minutes five days a week and move your body regularly. I recommend getting 10 to 15K steps in a day if you can. Add resistance and strength training to your routine.

Remove Toxins

Toxin overload can lead to mast cell activation, histamine intolerance, chronic inflammation, and related chronic symptoms. It’s critical that you lower your daily exposure to environmental toxins. Choose purified water over tap water. Use a high-quality air filtration system for better indoor air. Choose natural, organic, and homemade cleaning, personal hygiene, and beauty products instead of conventional brands loaded with chemicals. Choose glass, bamboo, wood, organic cotton, silicon, and other natural alternatives instead of plastic. Avoid BPA plastic completely. Choose organic food whenever possible and avoid overly processed packaged foods. If you must buy non-organic produce, follow the Dirty Dozen, Clean 15 list, and always wash and peel non-organic vegetables and fruits.

Final Thoughts

If you’ve taken anything from this article, I hope it is something along the lines of how complex and multifactorial these diseases are, and no one treatment is going to be effective for everyone. The good news is most of the time, this trifecta is very manageable. The bad news is it’s very individualized, and it may be a process of trial and error in figuring out what works best for you and your needs. Some people require medication and some don’t. Some have to be a low histamine diet for longer than others. The key is getting your body healthier, so you can tolerate more of the foods you love with natural mast cell stabilizers and no medications.

If you are dealing with symptoms of histamine intolerance, MCAS, POTS, or EDS, I invite you to schedule a consultation with us. We can help identify the root cause of your condition and recommend a personalized treatment plan to repair your body and regain your health and well-being. Schedule your consultation here. I also recommend that you check out my Histamine Online Program.