When Mast Cells Drive POTS: Understanding the MCAS Connection
Many people living with postural orthostatic tachycardia syndrome (POTS) spend years searching for answers about why their symptoms began—and why they persist. While POTS can be linked to a variety of causes, one underlying driver is often overlooked: mast cell activation syndrome (MCAS).
When the Immune System Fuels POTS
POTS is often described as an autonomic nervous system (ANS) disorder, characterized by symptoms such as rapid heart rate upon standing, lightheadedness, fatigue, and brain fog. But research increasingly shows that for some people, immune system dysfunction plays a central role.
In particular, mast cells—a type of immune cell—can become overactive. When this happens, they release chemical mediators like histamine, prostaglandins, and tryptase. These substances can:
Widen blood vessels, leading to blood pooling in the lower body
Trigger racing heart rate (tachycardia) as the body compensates
Contribute to dizziness, fatigue, and brain fog, which are core symptoms of POTS
For these individuals, POTS is not only an autonomic problem—it’s also an immune-driven condition.
MCAS Doesn’t Always Look Like Allergies
One reason MCAS can be missed is that it doesn’t always present in the classic way. People often expect mast cell issues to show up as skin symptoms like hives, rashes, or swelling. While that’s true for some, others experience more subtle or systemic symptoms—like gastrointestinal (GI) issues, headaches, or changes in heart rate or blood pressure—without any visible skin reactions.
This variability can make MCAS harder to recognize, but also more important to consider in many POTS cases.
Treating MCAS Can Improve POTS
The good news? When underlying MCAS is identified and treated, POTS has the potential to improve—sometimes significantly. Treatment approaches vary, but often involve a combination of:
Trigger avoidance (certain foods, environmental factors, or temperature extremes)
Histamine blockers or other mast cell–stabilizing medications prescribed by a healthcare provider
Dietary modifications to reduce histamine load
Careful pacing and symptom tracking to identify patterns
While MCAS may not be involved in every case of POTS, recognizing the connection if it does exist can be a critical step in creating a more effective treatment plan.
If you have POTS and standard treatments haven’t brought enough relief, it might be worth talking to your healthcare provider about whether MCAS could be contributing to your symptoms. Understanding and addressing the immune system’s role could open the door to better management and improved quality of life.
Want more tips?
Subscribe to Dr. Gould’s Neurenity Notes Newsletter—a free, supportive newsletter that breaks down MCAS symptoms, clarifying the confusion around diagnosis and which clinicians treat it, and provides tools for navigating the condition delivered to your inbox on a regular basis.
Download the Mini POTS Toolkit—a free guide created by Dr. Gould that breaks down frequently overlooked POTS symptom triggers and tools for managing them with confidence.
PMID: 32328892; PMID: 39165715; PMID: 29326369; PMID: 15710782
Disclaimer: This blog post is for informational purposes only and shall not be construed as behavioral health or medical advice. It is not intended or implied to supplement or replace treatment, advice, and/or diagnosis from your own qualified healthcare provider.