Is Two Better Than One?: The MCAS & POTS Connection

I was looking for quotes for this blog post when I came across this one from the movie  Contact, “Why build one when you can build two at twice the price?” Translated to chronic illness terms, I think it could go something like this: Why have one syndrome, when you can have two with twice the symptoms! Recently more doctors and researchers have observed the undeniable connection between Mast Cell Activation Syndrome (MCAS) and Postural Orthostatic Tachycardia Syndrome (POTS), so this pseudo-quote is a bit comical because if you have MCAS, there’s a good chance you have POTS as well, so you can’t just have one syndrome. Maybe that fell flat with you, but whatever. Let’s just continue onward.

If you’re reading this, maybe you have MCAS and/or POTS, or maybe you’re just curious about what these two syndromes have in common. Either way, let’s go over some definitions so everyone’s on the same page about everything.

What is Mast Cell Activation Syndrome?

Retrieved from

MCAS is a type of mast cell disorder. Mast cells are a type of white blood cell that everyone has and they exist in many tissues in the body. They help with things such as defense against microbes and parasites, blood vessel creation, wound healing, clotting, and regulation of reproductive activities. Mast cells release mediator chemicals to carry out their functions. However, in people with MCAS, their mast cells inappropriately release mediator chemicals which cause adverse symptoms like fatigue, inflammation, swelling, anaphylaxis, hives, GI issues, food sensitivities, etc. MCAS patients’ mast cells can release mediator chemicals in response to triggers such as food, scents, temperature, or physical and emotional stress. But they can also just release mediator chemicals for no reason at all.

What is Postural Orthostatic Tachycardia Syndrome?

Retrieved from

POTS is a form of dysautonomia, which is a dysfunction of the autonomic nervous system. The autonomic nervous system controls automatic functions in your body that you don’t consciously have to think about like heartbeat, breathing, digestion, etc. People with POTS experience symptoms when upright due to an increase in heart rate of 30+ beats per minute (40+ bpm for children and adolescents) or over 120bpm upon standing. Symptoms include fatigue, shortness of breath, dizziness, lightheadedness, nausea, blurred vision, and fainting, to name a few. Since POTS is a form of dysautonomia and your autonomic nervous system controls a lot of things, symptoms can be very diverse.

The Relationship Between MCAS & POTS

Ok, we have the basics, so what now? Interestingly enough, many doctors see that patients with both POTS (or another form of dysautonomia) and MCAS tend to fall on a spectrum, with one syndrome being more severe than the other. I definitely relate to this as my MCAS is worse than my POTS, but I know some people who are the opposite.

Dsyautonomia, MCAS spectrum
Many people with both POTS and MCAS fall on a spectrum, with one syndrome being more severe than the other.

However, this does not mean that everyone with POTS has MCAS, and vice versa. But because of the amount of patients with both syndromes, it seems pretty safe to say coincidence is not the sole factor at play. Although the exact number of how many people have both MCAS and POTS is unknown, the co-morbidity (occurrence of multiple chronic illnesses in a patient) of the two syndromes is evident.  There isn’t much concrete evidence as to why this is the case, but new research sheds light on this question. Here are the main points:

1. Nerves have receptors that can be activated by mast cell mediator chemicals

Inkednerve, mast cell, and symptoms_LI.jpg
Mast cell mediator chemicals can activate receptors on nerves, resulting in symptoms present in POTS. Retrieved from

The receptors TRPV1 and TRPA1 located on nerves can be activated by mast cell mediator chemicals like histamine, bradykinin, and prostaglandin. TRPV1 is responsible for the detection and regulation of body temperature while TRPA1 helps with sensory processing. Therefore, if mast cells are inappropriately releasing mediator chemicals, they are inappropriately activating sensory channels such as TRPV1 and TRPA1 on nerves, which is resulting in POTS/dsyautonomia symptoms.

In addition, it was found that nerve biochemical properties can actually change after allergic reactions. This may be why, in some patients, there is a delayed onset of POTS symptoms after resolution of typical allergic symptoms from a MCAS flare.

2. Mast cells can be activated by nerve stimulation

artery, mc, nerve
A microscopic image showing the closeness of arteries, nerves, and mast cells in the human body (a = artery, n = nerve, m = mast cell). Retrieved from

Nerves and mast cells are physically very close together in the body, specifically membrane to membrane (as seen in the picture above). There are specific substances in nerves that can directly induce mast cell degranulation (the process by which mast cells release mediator chemicals from their granules). In addition, scientists recently discovered that the immunoglobulin protein, SgIGSF not only helps bind mast cells and nerves together, but also can increase the communication between mast cells and nerves. In other words, there is something physically and chemically connecting nerves and mast cells so that nerve stimulation can result in greater activation of mast cells.

What does all of this mean?

Honestly, not much… right now. However, the fact that scientists are researching the relationship between MCAS and POTS means we’re on the right track. Further research into the co-morbidity of these syndromes can not only help doctors better understand the relationship between MCAS and POTS, but also potentially find ways to treat both of these syndromes, whether occurring together or separately.

If you have a diagnosis of MCAS or POTS, I would encourage you to look into the other syndrome. You may not have it, but I think it’s worth it to check. MCAS and POTS have so many overlapping symptoms so you may actually have both but just don’t know. For more information about the diagnostic criteria for POTS, go here. For MCAS, look at Table 2 in this journal article. This diagnostic criteria accounts for more chemical mediators than just tryptase, however there are other diagnostic criteria that are more stringent. It is important to note that just because your MCAS labs come back negative doesn’t mean you can rule out MCAS. The lab tests are very finicky, so sometimes they need to be performed multiple times (and during a MCAS flare) before positive results come back.

There are treatment options out there for both of these conditions, albeit not the most effective in some cases. That’s why research is so important–so doctors can understand the mechanisms behind MCAS and POTS and figure out better ways to treat them//


For more information about MCAS, check out the links on my “Chronic Illness Resources” page or read more on my “What is MCAS?” page. For more information about POTS, check out Dysautonomia International.

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