When POTS and MCAS Collide: Understanding the Overlap in Dysautonomia
- Angela Ashton Author
- Mar 2
- 8 min read
Updated: Mar 16
Living with a chronic invisible illness can feel isolating — especially when diagnoses overlap. Two conditions that frequently intersect are MCAS and POTS, both forms of dysautonomia that can profoundly affect daily life. Understanding how they connect can help patients recognize patterns, seek appropriate care, and feel less alone.
What Is Dysautonomia?
Dysautonomia is an umbrella term describing disorders of the autonomic nervous system (ANS) — the system that regulates heart rate, blood pressure, digestion, temperature control, and more. When the ANS malfunctions, the body struggles to regulate itself automatically.
Two commonly overlapping forms include:
Postural Orthostatic Tachycardia Syndrome (POTS)
Mast Cell Activation Syndrome (MCAS)
Though they arise from different mechanisms, they frequently coexist — and can amplify each other’s symptoms.
What Is POTS?
POTS is a condition where the heart rate increases excessively upon standing.
Diagnostic criteria generally include:
A sustained heart rate increase of 30+ beats per minute (40+ in adolescents) within 10 minutes of standing
Symptoms of orthostatic intolerance without a significant drop in blood pressure
Common symptoms include:
Rapid heartbeat (tachycardia)
Dizziness or lightheadedness
Fatigue
Brain fog
Blood pooling in the legs
Exercise intolerance
Nausea
POTS is not simply “being out of shape.” It is a neurological and circulatory regulation disorder.
What Is MCAS?
MCAS involves inappropriate activation of mast cells — immune cells responsible for releasing chemicals like histamine in response to threats.
When mast cells overreact, they release mediators inappropriately, causing multisystem symptoms such as:
Flushing
Hives or itching
Gastrointestinal distress
Low blood pressure or lightheadedness
Heart palpitations
Headaches
Anaphylactoid reactions
Unlike classic allergies, MCAS reactions may not always have a clear trigger.
The Overlap: Why Do MCAS and POTS Co-Occur?
Research and clinical experience show a significant subset of POTS patients also have MCAS. While exact numbers vary, the overlap is substantial enough that many autonomic specialists screen for both.
Here’s why they may intersect:
1. Mast Cell Mediators Affect Blood Vessels
Mast cells release substances like histamine, prostaglandins, and leukotrienes that:
Dilate blood vessels
Increase vascular permeability
Lower blood pressure
In POTS, blood vessel regulation is already impaired. If mast cell mediators cause additional dilation, blood pooling worsens — triggering tachycardia as the body tries to compensate.
This can intensify:
Dizziness
Rapid heart rate
Brain fog
Presyncope
2. Shared Triggers
Both conditions can flare with:
Heat
Stress
Hormonal changes
Illness
Exercise
Certain foods
A patient may believe they are having a “POTS flare,” when in reality mast cell activation is driving the worsening symptoms — or vice versa.
3. Hyperadrenergic Symptoms
Some POTS patients have a subtype called hyperadrenergic POTS, where adrenaline levels are elevated. Mast cell mediators can stimulate sympathetic nervous system activity, further driving:
Shakiness
Anxiety-like symptoms
Palpitations
Blood pressure fluctuations
The feedback loop can make symptoms feel dramatic and unpredictable.
4. Connective Tissue Links
There is also a recognized association between:
Ehlers-Danlos syndrome (especially the hypermobile type)
POTS
MCAS
Connective tissue abnormalities may affect blood vessel integrity and immune regulation, creating a “trifecta” presentation in some patients.
There is also a well-recognized clinical association between Ehlers-Danlos syndrome (EDS)—particularly the hypermobile type (hEDS), postural orthostatic tachycardia syndrome (POTS), and mast cell activation syndrome (MCAS). Many clinicians and researchers observe that these conditions frequently co-occur in the same patients, sometimes referred to informally as the “trifecta.”
Why these conditions may cluster
I. Connective tissue and vascular integrity
In hypermobile EDS, abnormalities in collagen and extracellular matrix structure can lead to increased tissue laxity, including within the vasculature. This may contribute to:
Excessive venous pooling
Reduced venous return when upright
Compensatory tachycardia
These hemodynamic changes are thought to increase susceptibility to orthostatic intolerance and POTS in individuals with hEDS.
II. Autonomic nervous system vulnerability
Connective tissue differences may also affect the mechanical environment of autonomic nerves and baroreceptors. Proposed mechanisms include:
Impaired vascular tone regulation
Altered baroreflex sensitivity
Increased sympathetic compensation
This can promote the dysautonomic patterns commonly seen in POTS.
III. Mast cell involvement and immune signaling
Mast cells reside throughout connective tissues and around blood vessels. In patients with MCAS, inappropriate mast cell mediator release (e.g., histamine, prostaglandins, tryptase) may contribute to:
Vasodilation and blood pressure variability
Flushing and vascular reactivity
GI and systemic inflammatory symptoms
Amplification of autonomic instability
Some researchers hypothesize that connective tissue differences in hEDS may influence mast cell behavior or tissue microenvironment, although this relationship is still under investigation.
IV. Shared symptom amplification
When these conditions coexist, patients may experience overlapping and mutually reinforcing symptoms, such as:
Orthostatic intolerance
Fatigue
Brain fog
GI dysmotility
Headaches
Flushing and hypersensitivity reactions
Chronic pain and hypermobility
The interaction between vascular laxity, autonomic compensation, and mast cell mediator effects may create a complex, multisystem presentation.
Important clinical note
While the EDS–POTS–MCAS association is widely reported in clinical practice and patient populations, causality has not been definitively established, and mechanisms remain an active area of research. Not every patient with one condition will develop the others.
How Patients Experience the Overlap
People with both conditions often report:
Feeling worse after meals (mast cell mediator release + blood shifting to digestion)
Flushing with tachycardia
Random adrenaline surges
Severe fatigue disproportionate to activity
Sensitivity to medications
Symptoms may shift day to day, making the condition hard to predict and difficult to explain. Living with both MCAS and POTS can be uniquely challenging because symptoms often overlap, fluctuate, and amplify one another in ways that are difficult to predict or explain. Many people find themselves managing waves of dizziness, tachycardia, flushing, fatigue, brain fog, and gastrointestinal distress that can shift from hour to hour. This layered presentation is not only physically exhausting but can also be emotionally taxing, especially when the full picture isn’t immediately visible to others. Patients navigating both conditions are often doing an enormous amount of behind-the-scenes regulation and adaptation each day, and their experience deserves to be met with compassion, validation, and thoughtful, coordinated care, not only from their physicians, but family and friends as well.
Diagnosis Challenges
Both POTS and MCAS are underrecognized. Many patients:
Are misdiagnosed with anxiety
Wait years for proper evaluation
See multiple specialists before receiving answers
Because there is no single, simple test that definitively captures MCAS, and because POTS requires careful, properly performed orthostatic vital sign testing, diagnosis often depends heavily on clinical awareness and pattern recognition. For many patients, this means a long and discouraging journey of symptoms that don’t neatly fit into one specialty box, normal routine labs, or being told “everything looks fine” while their daily functioning is clearly impacted. The uncertainty can be exhausting and, at times, deeply invalidating.
This is why seeing a clinician who is familiar with autonomic disorders and mast cell conditions is so important. Experienced providers are more likely to recognize the nuanced symptom patterns, perform appropriate orthostatic evaluations, and consider mast cell involvement even when standard tests are inconclusive. Compassionate, knowledgeable care can significantly shorten the path to meaningful support, helping patients feel seen, believed, and more effectively guided toward stabilization and improved quality of life.
Treatment Considerations
Treatment often requires addressing both conditions simultaneously.
For POTS:
Increased fluids and electrolytes
Compression garments
Graded exercise (when tolerated)
Medications to regulate heart rate or blood vessel tone
For MCAS:
H1 and H2 antihistamines
Mast cell stabilizers
Identifying triggers
Low-histamine dietary adjustments (in some cases)
When mast cell activation is controlled, some patients notice improved POTS stability.
The Bigger Picture
The overlap between MCAS and POTS illustrates how interconnected the immune and nervous systems are. The autonomic nervous system influences immune responses — and immune mediators influence autonomic tone.
For patients, recognizing the overlap can:
Validate confusing symptom patterns
Reduce self-blame
Improve treatment outcomes
Most importantly, it reinforces this truth:
You are not imagining it. These conditions are real, physiological, and increasingly recognized.
If you suspect overlap between POTS and MCAS, consider:
Tracking symptoms alongside triggers
Noting patterns after food, heat, stress, or standing
Seeking evaluation from an autonomic or mast cell–knowledgeable clinician
Chronic illness is complex — but understanding the connections can be empowering.
Because the EDS–POTS–MCAS overlap involves multiple body systems and often fluctuating symptoms, it can be difficult for others to fully understand what patients are experiencing. Family and friends may see someone who “looks fine” on the outside while struggling significantly day to day, which can lead to unintentional minimization or confusion. Even many healthcare providers find this presentation challenging, as it sits at the intersection of connective tissue biology, autonomic regulation, and immune signaling—areas that are often treated in separate specialties. This complexity can contribute to delayed recognition, fragmented care, and understandable frustration for patients navigating the path to diagnosis and effective support.
If you’re living with both POTS and MCAS, or the trifecta including EDS, you know the flares don’t always follow rules. One day it’s dizziness and racing heart; the next it’s flushing, nausea, adrenaline surges, or crushing fatigue — sometimes all at once. It can feel unpredictable, frustrating, and at times even frightening. But your symptoms are not random, and they are not “just anxiety.” They are the result of two very real, very physical systems interacting in complex ways. Learning that there is a connection — that there is a reason your body reacts the way it does — can be deeply validating. You are not overreacting and it's not all in your head. You are navigating a complicated overlap of conditions that deserve understanding, patience, and proper care. And even on the hardest flare days, this reality matters and deserves to be recognized.
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The Path Back to Safety is a grounded, compassionate guide for anyone living with chronic illness—especially when symptoms don’t fit neatly into a single diagnosis. Rather than treating conditions in isolation, the book explores how many chronic illnesses overlap, interact, and often stem from shared underlying patterns in the nervous system, immune system, hormones, and stress response.
It thoughtfully weaves together conditions such as chronic fatigue syndrome, fibromyalgia, long COVID, Lyme and post-viral syndromes, MCAS, POTS, dysautonomia, autoimmune and inflammatory conditions, thyroid and hormonal imbalances, connective tissue disorders like EDS, chronic pain, neurological symptoms, mast cell issues, histamine intolerance, anxiety rooted in the body, and unexplained multisystem symptoms. Through this lens, readers begin to see why treatments often fail when the body is addressed in pieces instead of as a whole.
Angela Ashton explains how these conditions frequently coexist, amplify one another, and cycle through the same pathways—nervous system dysregulation, chronic inflammation, immune overactivation, trauma responses, and loss of internal safety. The book offers clarity, validation, and a unifying framework that helps readers understand why their symptoms make sense together—and how healing becomes possible when safety, regulation, and connection are restored.
This is not a one-condition book. It’s a map for anyone whose illness has been complex, misunderstood, or labeled “too much,” offering a calm, holistic path forward when the body has been living in survival mode for far too long.
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Medical Disclaimer
The information provided in this article is for educational and informational purposes only and is not intended as medical advice, diagnosis, or treatment. POTS and MCAS are complex medical conditions that require individualized evaluation and management by a qualified healthcare professional. Always consult your physician or a licensed medical provider regarding any questions you have about your symptoms, treatment options, medications, or changes to your care plan. Never disregard professional medical advice or delay seeking care because of something you have read here. If you are experiencing a medical emergency, seek immediate medical attention.
This made sense to me. Love the book also.
Awesome information, thank you.