Mast Cell Activation Syndrome vs POTS: Are You Treating the Wrong Condition?

When your body suddenly feels like it’s working against you—your heart races, you feel dizzy, nauseous, or exhausted even after standing for a few minutes—it can be confusing and frustrating. For many, these symptoms lead to a diagnosis of Postural Orthostatic Tachycardia Syndrome (POTS).
But what happens when treatments for POTS don’t seem to help as expected? Sometimes, the real issue might be another closely related condition: Mast Cell Activation Syndrome (MCAS).

Let’s break down what each condition is, how they overlap, and what you can do to make sure you’re getting the right diagnosis and treatment.

What Is POTS?

POTS (Postural Orthostatic Tachycardia Syndrome) is a disorder of the autonomic nervous system—the part of your body that manages functions like heart rate, blood pressure, and digestion without you thinking about it.

When someone with POTS stands up, their heart rate increases dramatically (by 30 beats per minute or more) without a drop in blood pressure. This can cause symptoms such as:

• Lightheadedness or fainting
• Rapid heartbeat (palpitations)
• Fatigue and weakness
• Brain fog or trouble concentrating
• Nausea or bloating
• Cold hands and feet

Many people with POTS are young women, and the condition often appears after an illness, injury, or hormonal change. While there’s no cure, lifestyle changes and medications can help manage the symptoms.

What Is Mast Cell Activation Syndrome (MCAS)?

Mast Cell Activation Syndrome is a condition where the body’s mast cells—a type of immune cell—release too many inflammatory chemicals (called mediators) into the bloodstream.

Mast cells are meant to protect you from infections or allergic reactions. But in MCAS, they overreact to triggers like certain foods, heat, stress, or even strong smells, causing a wide range of symptoms:

• Flushing, itching, or hives
• Swelling or feeling of throat tightness
• Abdominal pain, diarrhea, or nausea
• Headaches and brain fog
• Rapid heartbeat or low blood pressure
• Anxiety or sense of “impending doom”

Because these symptoms vary from day to day, MCAS is often mistaken for allergies, anxiety, or even POTS.

Why MCAS and POTS Often Overlap

Many people are surprised to learn that MCAS and POTS often occur together. In fact, studies suggest that up to 30–40% of patients with POTS also have signs of MCAS, according to preliminary studies or select populations.

Here’s why the two are linked:

1. Shared Autonomic Dysfunction:
   Both conditions affect the autonomic nervous system. Mast cell mediators can cause changes in blood vessel tone and volume—triggering the dizziness and rapid heartbeat seen in POTS.
2. Inflammatory Connection:
   When mast cells release histamine and other chemicals, they can lead to inflammation and vascular dilation (widening of blood vessels). This contributes to the “pooling” of blood in the legs that worsens POTS symptoms.
3. Common Triggers:
   Heat, stress, exercise, or certain foods can flare both MCAS and POTS symptoms.
4. Genetic and Environmental Factors:
   Some researchers believe that a genetic predisposition to immune sensitivity may underlie both disorders.

The Diagnostic Challenge: Similar Symptoms, Different Causes

MCAS and POTS can look almost identical at first glance.
Here’s how their symptoms compare:

Because the symptoms overlap so much, many patients are treated for POTS alone, missing the mast cell component that might actually be driving the dysfunction.

Could You Be Treating the Wrong Condition?

If you’ve been diagnosed with POTS but your symptoms don’t fully improve—or if new allergic-type symptoms appear—you may want to ask your doctor about testing for Mast Cell Activation Syndrome.

Here are a few clues that MCAS could be part of your picture:

• POTS medications (like beta blockers or salt tablets) help only a little.
• You experience unexplained flushing, rashes, or itching.
• You react to certain foods, smells, or medications.
• You have frequent gastrointestinal distress that doesn’t respond to diet changes alone.
• You notice improvement when using antihistamines or mast cell stabilizers.

Because both conditions can coexist, treating MCAS can sometimes dramatically improve POTS symptoms as well.

Diagnosing MCAS and POTS

For POTS:

Diagnosis usually involves:

• A Tilt Table Test or standing test to measure heart rate and blood pressure changes.
• Blood work to rule out thyroid disease, anemia, or adrenal problems.
• Review of symptoms lasting at least six months.

For MCAS:

Diagnosis can be trickier. Doctors may order:

• Blood or urine tests to measure mediators like tryptase, histamine, or prostaglandins.
• Symptom diary tracking, noting possible triggers and flare patterns.
• Response to treatment, since improvement with antihistamines can help confirm suspicion.

A physician familiar with both conditions—often an allergist, immunologist, or autonomic specialist—can help distinguish between them.

How Treatment Differs Between POTS and MCAS

Treating POTS:

• Increase fluids and salt to raise blood volume.
• Compression garments to reduce blood pooling.
• Exercise therapy focusing on recumbent workouts like cycling or rowing.
• Medications such as beta blockers, fludrocortisone, or midodrine to regulate heart rate and blood pressure.

Treating MCAS:

• Avoid triggers (certain foods, heat, alcohol, or perfumes).
• Antihistamines (both H1 and H2 blockers).
• Mast cell stabilizers like cromolyn sodium.
• Low-histamine diet to reduce inflammation.
• Epinephrine for severe reactions (anaphylaxis).

Because mast cell activation can worsen autonomic instability, managing MCAS can indirectly help stabilize POTS symptoms.

The Overlap Approach: Treating Both Together

If you have both POTS and MCAS, treatment needs to address both autonomic balance and immune regulation. Here’s what a combined plan might look like:

1. Hydration and Electrolytes: Daily fluids with electrolytes to support circulation.
2. Trigger Management: Identify and minimize known mast cell triggers.
3. Dietary Adjustments: Adopt a low-histamine or anti-inflammatory diet.
4. Medication Coordination: Use antihistamines alongside POTS-friendly medications (with doctor approval).
5. Gentle Conditioning: Gradual exercise to build stamina without triggering flares.
6. Stress Management: Mindfulness, meditation, and breathing techniques can reduce both mast cell and autonomic overactivity.
7. Regular Follow-up: Continuous care with a specialist who understands both conditions is key.

Why Getting the Right Diagnosis Matters

Treating the wrong condition—or only part of it—can delay recovery and add unnecessary frustration.
Understanding whether MCAS, POTS, or both are present helps your medical team design a plan that truly fits your biology.

When MCAS is the missing piece:

• Symptoms may fluctuate wildly with no clear reason.
• Standard POTS medications may not fully work.
• Emotional well-being can suffer due to constant uncertainty.

But once the correct diagnosis is made and both conditions are addressed, many patients find significant improvement in energy, mental clarity, and overall quality of life.

When to See a Specialist

If you suspect you might have MCAS along with POTS, look for a doctor experienced in autonomic and immune disorders. A specialist can coordinate testing, manage medication combinations safely, and guide you through lifestyle changes that reduce flare-ups.

At clinics specializing in Dysautonomia and related conditions, like Diekman Dysautonomia, the focus is on listening to your story, identifying overlapping syndromes, and creating a treatment plan tailored to your unique situation.

Final Thoughts

POTS and MCAS share a complex, intertwined relationship. Both conditions can make everyday life challenging, but understanding how they interact opens the door to more effective treatment.

If your POTS care isn’t giving you the relief you hoped for, it doesn’t mean your symptoms are “in your head.” It might mean your mast cells are part of the problem.

By recognizing the connection between Mast Cell Activation Syndrome and POTS, patients and doctors can work together to target the real root cause—and move one step closer to better health and stability.