The Trifecta: POTS, EDS & MCAS in Neurodivergent Folk

Ehlers-Danlos Syndrome (EDS), Postural Orthostatic Tachycardia Syndrome (POTS), and Mast Cell Activation Syndrome (MCAS) are found to co-occur in neurodivergent (ND) folk. This highlights how deeply connected our immune, nervous, and connective tissue systems are.

Neurodivergence and The Trifecta

What Is Ehlers-Danlos Syndrome (EDS)?

Ehlers-Danlos Syndrome (EDS) is a group of 13 heritable connective tissue disorders. (1) Connective tissue acts as the glue that supports our joints, skin, organs, and blood vessels. In EDS, genetic variations change how this tissue is made, leading to widespread effects across the body. (1)

Hypermobile EDS (hEDS)

The most common type is hypermobile EDS (hEDS), for which the genetic cause remains unknown. (1) People with hEDS have joint hypermobility, meaning their joints move beyond the normal range. Some experience no pain, while others deal with joint instability, dislocations, sprains, and chronic pain. (1)

Because connective tissue is found throughout the body, symptoms can appear in the skin, gut, eyes, and cardiovascular system—not just the joints.

Common signs and symptoms of hEDS include:

• Bendy or double-jointed joints

• Frequent dislocations or sprains

• Chronic pain or fatigue

• Gut and bladder dysfunction

• Anxiety and poor proprioception

• TMJ (jaw pain), headaches, and migraines

• Poor wound healing and easy bruising

  

  EDS Symptom Wheel Source: https://www.ehlers-danlos.com/what-is-eds/

If you don’t meet the full diagnostic criteria for hEDS, you may be diagnosed with Hypermobility Spectrum Disorder (HSD)—a related condition treated in similar ways.

Around 80–88% of people with EDS also have POTS. (2,3)

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What Is POTS (Postural Orthostatic Tachycardia Syndrome)?

POTS is a form of dysautonomia, meaning dysfunction of the autonomic nervous system, which is the part of our body that controls automatic processes like heart rate, digestion, and temperature regulation. It’s most common in those assigned female at birth (AFAB) and often appears alongside EDS. (4,5)

The diagnostic criteria checks your heart rate and blood pressure from lying down for 10-15 minutes to standing up. If there is a sustained, increased heart rate of +30 beats per minute (bpm) in adults, or a heart rate that exceeds 120 bpm when standing, and an absence of a large drop in blood pressure in the first 3 minutes of standing, this may indicate you have POTS. This test is called the NASA lean test. If you do have a large blood pressure drop with the increased heart rate, this may indicate to you that you have orthostatic hypertension, which is another type of dysautonomia.

In someone who may not have POTS, when we stand upright, our body usually reacts to this change in blood volume in our head by increasing the blood pressure and constricting our blood vessels to get blood back to the brain. In POTS, this may not be the case, and our blood pressure does not compensate for the change in posture; therefore, our blood will pool downwards (in our legs), which can make us feel lightheaded.

POTS can be debilitating and affect your quality of life

Common POTS Symptoms

• Lightheadedness or fainting when standing

• Rapid heart rate or palpitations

• Brain fog, fatigue, and poor concentration

• Temperature dysregulation

• Digestive issues and nausea

• Bladder dysfunction

• Anxiety or feeling “on edge”

POTS can be triggered by viral infections (including COVID-19), concussions, hormonal changes, or major stress events. (4)

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What Is Mast Cell Activation Syndrome (MCAS)?

Mast Cell Activation Syndrome (MCAS) is an immune system condition involving over-reactive and hypersensitive mast cells. Mast cells are white blood cells responsible for allergy and inflammation responses. In MCAS, these cells release inflammatory chemicals (like histamine) too easily, reacting to real or perceived threats.

When a threat is perceived, our mast cells will degranulate, which leads to a release of chemical mediators (histamine, heparin, cytokines and growth factors) to elicit inflammatory responses throughout the body, which can then cause a variety of symptoms. Symptoms and the strength of symptoms can vary each day, depending on how much of the threat you are exposed to.

Mast cells are present everywhere in our body, including our vascular, nervous, digestive and skin systems, organs and tissues.

A Mast Cell Source: https://tmsforacure.org/overview/

Common MCAS Triggers

• Sensory stimuli: loud noises, strong smells, bright lights

• Environmental allergens: pollen, dust, pets

• Foods high in histamine or additives

• Hormonal changes

• Medications, caffeine, alcohol, and stress

Some MCAS Symptoms

• Flushing, rashes, or hives

• GI pain, reflux, nausea, diarrhoea, or constipation

• Fatigue, headaches, and brain fog

• Heart palpitations and anxiety

• Chronic pain, joint pain, or temperature intolerance

• Pelvic pain and painful periods

• Insomnia and difficulty concentrating

• More can be found here

Diagnosing MCAS is challenging because blood tests for histamine or tryptase are often unreliable unless taken during a flare. (6) Instead, doctors rely on clinical criteria and symptom patterns.

One study found that 66% of patients with EDS and POTS had symptoms consistent with MCAS. (7)

The Trifecta of chronic health conditions

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The Link Between Neurodivergence, EDS, POTS and MCAS

Research continues to reveal genetic and inflammatory overlaps between neurodivergence (autism, ADHD) and these chronic conditions.

Some examples of how these co-occuring conditions affect each other

• People with EDS are 7.4x more likely to be autistic and 5.6x more likely to have ADHD. (8)

• Between 32–74% of ADHDers and 13–53% of autistic individuals may experience hypermobility or EDS. (8)

  • The variation in percentage across these groups could be due to a misdiagnosis of other conditions found in this population, including Irritable Bowel Syndrome (IBS), Functional Neurological Disorder (FND), fibromyalgia and anxiety. (8)

• Mast cell activation may contribute to neuroinflammation, which may play a role in autism and ADHD development. (9,10,11)

  
  

Because neurodivergent individuals often experience chronic cumulative stress (especially if they have gone undiagnosed most of their life and have been expected to push through due to neurotypical and societal standards of functioning), sensory sensitivities, and interoceptive differences, symptoms may go unnoticed or misinterpreted for years, especially in women and AFAB individuals.

Additionally, trauma, illness, or burnout can trigger or worsen POTS and MCAS over time.

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Living With The Trifecta and Neurodivergence: Support Strategies

Managing these interconnected conditions requires a holistic, neuroaffirming, and quality-of-life approach rather than a purely symptom-focused one.

Practical Strategies

• Simplify medication routines: Use Webster packs or reminders

• Hydration and salt intake: Support blood volume for POTS

• Antioxidant and anti-inflammatory rich diet: Manage MCAS symptoms where appropriate and prioritising safe foods (a low histamine diet may be warranted)

• Gentle movement & pacing: Support joint stability in EDS

• Compression garments: Improve circulation (if sensory-friendly)

• Support executive functioning: Simplifying nutritional intake and medication use

  
  

Allied Health & Medical Support

A multidisciplinary team can make a world of difference. This may include:

• GP

• Physiotherapist or exercise physiologist

• Dietitian

• Occupational therapist

• Psychologist

• Rheumatologist

• Cardiologist

• Neurologist

• Gastroenterologist

• Geneticist

• Support workers or care coordinators

Ready for neuroaffirming nutrition support?

If you’re living with neurodivergence and the trifecta, you don’t have to figure it out alone.

As a Credentialed Eating Disorder Dietitian I provide neuroaffirming, evidence-based support for people with chronic illness, neurodivergence, and complex medical needs. Together, we can work toward nourishment, symptom management, and improved quality of life at your pace.

Book an appointment today to start working together in a supportive, validating space.

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Helpful Resources

• The Ehlers-Danlos Society

• EDS GP Toolkit (Australia)

• Standing Up to POTS

• POTS Foundation Australia

• Mastocytosis Australia

• NASA Lean Test for POTS

• Mast Cell Mediator Release Questionnaire

• The Neurodivergent Woman Podcast

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References

1. The Ehlers-Danlos Society. (n.d.). What is EDS? https://www.ehlers-danlos.com/what-is-eds/

2. Standing Up to POTS. (n.d.). Ehlers-Danlos syndrome and POTS. https://www.standinguptopots.org/EDS

3. Brock, I., Chopra, P., Maitland, A., & Francomano, C. (2021). Frequency and co-occurrence of comorbidities in the Ehlers-Danlos syndromes. Molecular Genetics and Metabolism, 132(Supplement 1), S194. https://doi.org/10.1016/S1096-7192(21)00387-5

4. POTS Foundation Australia. (n.d.). POTS for practitioners. https://potsfoundation.org.au/pots-for-practitioners/

5. Csecs, J. L. L., Iodice, V., Rae, C. L., Brooke, A., Simmons, R., Quadt, L., et al. (2022). Joint hypermobility links neurodivergence to dysautonomia and pain. University of Sussex. https://hdl.handle.net/10779/uos.23487188.v1

6. Afrin, L. B., Self, S., Menk, J., & Lazarchick, J. (2017). Characterization of mast cell activation syndrome. The American Journal of the Medical Sciences, 353(3), 207–215. https://doi.org/10.1016/j.amjms.2016.12.013

7. Farley, M., Estrada-Mendizabal, R. J., Gansert, E. A., Voelker, D., Marks, L. A., & Gonzalez-Estrada, A. (2025). Prevalence of mast cell activation disorders and hereditary alpha tryptasemia among patients with postural orthostatic tachycardia syndrome and Ehlers-Danlos syndrome: A systematic review. Annals of Allergy, Asthma & Immunology, 135(1), 97–102. https://doi.org/10.1016/j.anai.2025.03.022

8. Theoharides, T. C., Kavalioti, M., & Tsilioni, I. (2019). Mast cells, stress, fear and autism spectrum disorder. International Journal of Molecular Sciences, 20(3611), 1–16. https://doi.org/10.3390/ijms20153611

9. Theoharides, T. C., Stewart, J. M., Panagiotidou, S., et al. (2016). Mast cells, brain inflammation and autism. European Journal of Pharmacology, 778, 96–102. https://doi.org/10.1016/j.ejphar.2016.02.030

10. Song, Y., Lu, M., & Yuan, H., et al. (2020). Mast cell-mediated neuroinflammation may have a role in attention deficit hyperactivity disorder: Review. Experimental and Therapeutic Medicine, 20, 714–726. https://doi.org/10.3892/etm.2020.8743

11. TMS for a Cure. (n.d.). Overview: Mast cell activation syndromes. https://tmsforacure.org/overview/#mast-cell-activation-syndromes

12. Australasian Society of Clinical Immunology and Allergy (ASCIA). (2025). Mastocytosis FAQ. https://www.allergy.org.au/images/pc/ASCIA_PC_Mastocytosis_FAQ_2025.pdf

13. Freeman, R., Wieling, W., Axelrod, F. B., Benditt, D. G., Benarroch, E., Biaggioni, I., ... & Stewart, J. M. (2011). Consensus statement on the definition of orthostatic hypotension, neurally mediated syncope, and the postural tachycardia syndrome. Autonomic Neuroscience: Basic and Clinical, 161(1–2), 46–48. https://doi.org/10.1016/j.autneu.2011.02.004

14. Afrin, L. B., Butterfield, J. H., Raithel, M., & Molderings, G. J. (2016). Often seen, rarely recognized: Mast cell activation disease – A guide to diagnosis and therapeutic options. Annals of Medicine, 48(3), 190–201. https://doi.org/10.3109/07853890.2016.1161231