Have you ever noticed that you have hypermobile joints or that you are too flexible? Do you injure yourself easily or are experiencing pain from activities that are easy for others? You may have Ehlers-Danlos syndrome (EDS).

Recent research suggests that EDS and mast cell activation syndrome (MCAS) can co-occur and affect one another. Your mast cells may hold the answer to some of your symptoms your EDS diagnosis can’t explain. Recognizing the connection between EDS and MCAS may be the key to understanding your symptoms and finding the best treatment options.

In this article, I will discuss the connection between EDS, hypermobility and MCAS. You will learn what EDS and MCAS are and what their symptoms are. You will understand how EDS and MCAS may affect one another. Finally, I will offer some natural strategies to help improve your health.


What Are Ehlers-Danlos Syndromes

Ehlers-Danlos syndromes (EDS) are a group of 13 conditions. Most of these are inherited conditions. The most common type, hypermobile EDS (hEDS), might be inherited like other forms, but so far no genes have been isolated connected to this hEDS. This means that while we are able to use genetic testing to diagnose other types of EDS, we can’t actually test for hEDS (1, 2).

EDS is characterized by abnormal collagen function As a result, EDS can affect your connective tissues, including your joints, bones, skin, blood vessels, and organs. EDS doesn’t have a cure (1, 2).


Types of EDS

There are 13 types of EDS with the hypermobile and classical types being the most common ones (1, 2, 3). Each type of EDS is different, with its distinct set of features and diagnostic criteria. Some types have specific genetic markers that allow for diagnosis. However, the genetic mutations for some forms of EDS have not yet been discovered.

For example, in hypermobile EDS, the diagnosis is made clinically since the genetics is unknown and it is mainly characterized by joint hypermobility, joint instability, and chronic pain. Classical and dermatosparaxis EDS have skin-centric symptoms, such as extreme skin flexibility. Vascular EDS affects your cardiovascular system, causing arterial fragility, organ fragility, and extensive bruising (1, 2).


The 13 types of EDS include:

  • Hypermobile
  • Classical
  • Classical-like
  • Cardiac-valvular
  • Vascular
  • Arthrochalasia
  • Kyphoscoliotic
  • Brittle cornea
  • Spondylodysplastic
  • Musculocontractural
  • Myopathic
  • Dermatosparaxis
  • Periodontal


Features of EDS

Though each case and type of EDS is different, certain features, including joint hypermobility, skin hyperextensibility, and tissue fragility are common among several types of EDS.

  • Joint hypermobility: If you have joint hypermobility it means that your joints have a greater range of motion than the general population. This may cause joint instability, joint subluxations, sprains, dislocations, other injuries, acute pain, and chronic pain. The most common joints involved in EDS are fingers, knees, and elbows, but it can occur in other joints too.
  • Skin hyperextensibility: If you have skin hyperextensibility, it means that your skin is very stretchy and can be stretched beyond what’s considered the normal range. Certain types of EDS only have mild skin hyperextensibility (1.5 – 2 cm), others have more severe cases (over 2 cm). With skin hyperextensibility, you may exhibit other skin issues, such as thin skin, skin fragility, poor wound healing, scarring, or unusual skin texture.
  • Tissue fragility: If you have tissue fragility, it means that your tissues and organs are more vulnerable to damage. This means it shows up as bruising easily, poor wound healing, or severe fragility of your blood vessels, skin, gums, abdominal organs, eyes, or bones.


Symptoms of Hypermobile EDS (hEDS)

Hypermobile EDS is one of the most common forms of EDS accounting for about 80 to 90% of cases. It is also the most commonly linked to mast cell activation syndrome (1, 2, 3).

Symptoms of hypermobile EDS include:

  • Loose joints
  • Bruising easily
  • Muscle fatigue
  • Chronic pain
  • Chronic degenerative joint disease
  • Premature osteoarthritis
  • Digestive issues like constipation
  • Dizziness and tachycardia associated with changes in position.
  • Pelvic floor issues
  • Bladder issues


What Is Mast Cell Activation Syndrome

Your mast cells are white blood cells located in your connective tissues, including your skin,, intestines, lungs, blood vessels, and lymph vessels. They play an important role in your immune system.

Your mast cells store histamine and other inflammatory mediators. When your body encounters an infection, allergen, toxin, or another trigger, they are there to act as a first responder. They will warn your immune system about the danger. Mast cells become activated in response to a trigger and release histamine or other inflammatory mediators.

Mast cells turn into a problem if they become overactive or dysregulated. Mast cells are a necessary part of your immune system and as long as they function normally, after a response to a trigger they will reset and wait for the next attack. However, dysfunctional mast cells are problematic and are at baseline activated even without an obvious trigger. In this case, they continue to release their mediators even if there is no real danger. This is Mast Cell Activation Syndrome (MCAS). MCAS can lead to widespread, chronic symptoms and health issues. (4, 5).


Symptoms of MCAS may include:

  • Hives
  • Rashes
  • Itching
  • Fatigue
  • Weakness
  • Migraines and headaches
  • Dizziness
  • Heart palpitations
  • Chest pain
  • Low blood pressure
  • High blood pressure
  • Digestive issues
  • Poor appetite
  • Weight loss or weight gain
  • Anxiety and/or Depression
  • Changes in vision
  • Frequent urination and incontinence
  • Menstrual irregularities
  • Pelvic pain


The Connection Between hEDS and MCAS

Let’s think about this for a moment. EDS is a condition that affects your connective tissues. Your mast cells are white blood cells located in your connective tissues. It makes sense that having EDS may affect your mast cells and mast cells may affect EDS. Research suggests that the two conditions may be connected. MCAS seems to be specifically common in hEDS and its variant, hypermobile spectrum disorder (HSD) (6, 7).

A 2017 review published in the American Journal of Medical Genetics has discussed the link between EDS and MCAS (8). Mast cells tend to attach to proteins, such as fibronectin and vitronectin, in the extracellular matrix. This interconnection between mast cells and these proteins may cause the increased production and release of proinflammatory cytokines (9).

According to a 2015 study published in the Journal of Allergy and Clinical Immunology, MCAS, EDS, and postural tachycardia syndrome (POTS) may be cluster conditions (10). Researchers found that 66% of participants with hEDS and POTS also had symptoms of MCAS. Research suggests that there is not only a potential link between EDS and MCAS, but between all these three conditions.

A 2016 article published in Nature Genetics indicated that mast cell activation might be connected to connective tissue diseases, such as EDS (11). They believe that the connection may be related to genetic issues.

Researchers looked at families and individuals with elevated baseline serum tryptase levels caused by a genetic condition known as hereditary alpha tryptasemia. Elevated levels are present in about 4 to 6% of the general population and have been linked to the triad of hEDS, POTS, and MCAS. The families identified for the study had germline duplications and triplications in the TPSAB1 gene, which may be responsible for elevated basal serum tryptase levels. Researchers found that those with three copies of α-tryptase had higher tryptase levels.

This suggests a gene-dose effect. Researchers also looked at individuals with a duplication of α-tryptase–encoding sequence in TPSAB1 and high tryptase. They found that there may be a connection between duplications in TPSAB1 and connective tissue disorders, such as EDS, dysautonomias, such as POTS, irritable bowel syndrome, and skin problems, commonly found in EDS.

A 2022 review published in Immunology Research has found that mast cell activation and histamine, and other mast cell mediators may play an important part in connective tissue integrity disruption and related multisystem health issues (7). The presence of inflammatory processes may explain the overlap between MCAS, hEDS, and HSD. Researchers recommend using a multidisciplinary approach when addressing EDS and considering looking at underlying mast cell issues as well.

A 2022 review published in AIMS Allergy and Immunology has also found an overlap between gastrointestinal issues, including abdominal pain, nausea, and hernias, and MCAS, EDS, and POTS (12).


Recommendations for hEDS and MCAS

Neither EDS nor MCAS has a known cure. However, there are certain strategies you may try to improve your condition. Here is what I recommend.


Reduce Your Triggers for Mast Cell Activation

A variety of environmental factors can trigger mast cell activation. Reducing your exposure to your triggers may significantly reduce your symptoms. Common triggers of mast cell activation may include allergens, toxins, chemicals, mold, heavy metals, viruses, bacteria, parasites and stress.

Avoid toxins, chemicals, heavy metals, and other environmental toxins. I recommend avoiding chemical-filled conventional cleaning, hygiene, body, and beauty products, and choosing organic, natural, and homemade alternatives. Reduce the use of plastics. Eat organic food whenever possible. Drink purified water to avoid toxins from city tap water or well water. Use a high-quality indoor air-filtration system for better indoor air quality, free from allergens, toxins, and mold. Remove any mold from your home. Reduce stress and anxiety.


Detoxify Your Body

Supporting your body’s detoxification pathways may help to remove chemicals, heavy metals, mold, other toxins, and microbes that may trigger mast cell activation. Exercising regularly supports detoxification through sweating and some people do well with infrared saunas as another way to sweat. Drink plenty of water to help the removal of toxin buildup through sweat and urine. Some people find using activated charcoal or other binders may help absorb and remove toxins (13). Glutathione may protect your mitochondria from oxidative stress and damage (14).


Follow the Dempsey Diet

I recommend following the Dempsey Diet. This is an anti-inflammatory, nutrient-dense food plan. Remove inflammatory foods, including refined sugar, refined oils, additives, artificial ingredients, and highly processed foods. Follow a nutrient-dense diet focusing on good quality, grass-fed or pastured meat and poultry, and low carbohydrate vegetables and greens. Choose organic options whenever available. In general, avoiding sugar, and limiting fruit and starchy carbohydrates is helpful for MCAS and other chronic conditions I treat. You may also do well lowering your intake of histamine in your diet, however, it doesn’t work for everyone.


Reduce Stress

Certain lifestyle choices may trigger mast cell activation. I recommend reducing your stress levels and learning stress-management strategies. Improve your sleep hygiene. Get 7 to 9 hours of restorative sleep at night. Move your body regularly and spend time in nature. Overall, reducing your environmental toxin exposure is critical too.


Supplements for Mast Cell Activation

For some patients, natural mast cell stabilizers and natural antihistamines, including quercetin, curcumin, resveratrol, vitamin C, nettle leaf, luteolin, and DAO enzyme, can be helpful (15, 16, 17, 18, 19, 20, 21). I recommend speaking with your doctor before taking any supplements to ensure appropriate dosing and reduce the risk of side effects.


Medications for Mast Cell Activation

You may also benefit from taking medication for mast cell activation. Some examples of drug classes that are used for MCAS are antihistamines, mast cell stabilizers, leukotriene inhibitors, aspirin or other NSAIDS, and other agents that target the mast cell. Please, consult your doctor to see if you need medication and what medications are right for you.


Next Steps

If you are experiencing symptoms of MCAS, hEDS, or other chronic health issues, working with a functional medicine practitioner is one of the best ways to find the underlying causes of your symptoms and find the right treatment plan. At AIM Center for Personalized Medicine, we use a personalized approach to understanding your symptoms, finding the root of your health issues, and creating an individualized treatment plan to regain your health. Find out more about AIM here.