The POTS - MCAS Link

Mast Cell Activation Syndrome (MCAS) and Postural Orthostatic Tachycardia Syndrome (POTS) are more common among neurodivergent people. They can be hard to manage and often co-occur, alongside hypermobility/Ehler’s-Danlos Syndrome (EDS). These conditions share a number of symptoms, with at least 17 overlapping symptoms identified between POTS and MCAS, which can make getting a correct diagnosis challenging. These conditions can also feed into each other, with MCAS often triggering POTS flare-ups. Fortunately the opposite is also true, reducing mast cell activation can improve POTS symptoms.

Understanding the links between these conditions can aid in advocating for and accessing the care you need, and can improve management outcomes.

To better grasp how these conditions work together we need to understand the 3 different sub-sets of POTS. These are neuropathic (nerve damage) POTS, hypovolemic (low blood volume) POTS and hyperadrenergic (high noradrenaline/adrenaline) POTS. These different types of POTS can and often do co-occur. We often don’t fit neatly into diagnostic boxes and POTS can look different person to person.

1.Neuropathic POTS
Neuropathic POTS involves nerve damage in the autonomic nervous system. The autonomic nervous system takes care of body functions without our conscious control. Normally, these autonomic nerves help blood vessels narrow and prevent blood pooling in the abdomen, hands, and feet. Damage to these nerves reduces their ability to contract, leading to blood pooling. This can cause light headedness, dizziness, fatigue, and a rapid heart rate as the body tries to pump more blood to the brain.

What’s the link with MCAS?
Mast cells are often near nerve endings and can sensitize nerves, lowering their pain threshold. There’s growing evidence that mast cell activation may contribute to nerve damage over time, which can lead to small fibre nerve damage seen in neuropathic POTS.

2. Hypovolemic POTS
Hypovolemic POTS is marked by low blood volume. There may be low levels of hormones (renin and aldosterone) that ordinarily increase blood volume and blood pressure. When standing, insufficient blood returns to the heart, causing an increase in heart rate to ensure blood reaches the brain.

What’s the link with MCAS?
Activated mast cells release substances like histamine, which can make blood vessels more permeable. This causes fluid to leak from vessels, lowering blood volume. Hypermobile EDS may also contribute due to more elastic blood vessels.

3.Hyperadrenergic POTS
Hyperadrenergic POTS features high blood pressure and elevated noradrenaline. Noradrenaline is a neurotransmitter in the "fight or flight" response, which is overactive in this type of POTS. An excessive release of noradrenaline in response to stimuli (like a drop in blood volume on standing or stress) can trigger symptoms like increased heart rate, blood pressure, sweating, and panic.

What’s the link with MCAS?
Mast cell contents, particularly histamine, can trigger the release of noradrenaline causing a flare in POTS symptoms.

Mast cells influence POTS symptoms in other ways:

• Affecting the autonomic nervous system: Chronic mast cell activation can contribute to dysautonomia. Mast cell contents can impact autonomic control centres in the brain,  sensory nerve fibres, and dysregulate blood vessel constriction and dilation.

• Interfering with blood vessel tone: Mast cell substances like histamine can cause blood vessels to dilate or constrict, contributing to blood pooling.

• Contributing to overlapping symptoms: Mast cell activation can contribute to other overlapping symptoms like brain fog and gut issues. The gut houses one of the largest supplies of mast cells in the body and mast cell activation can significantly impact gut function. Mast cell contents often impact gut motility causing reflux, diarrhoea, bloating, cramping, nausea and vomiting. In the brain, mast cell activation is linked to brain fog, cognitive issues, sleep issues, fatigue, headaches, migraines and mental health concerns (commonly anxiety).

How does this aid management?

When these conditions coexist, as is often the case, treating just one often isn’t enough to bring real relief. For some, reducing mast cell activation can be the missing piece in managing POTS. Every person is different, and it can take time (and often a lot of self-advocacy) to find the management strategies that work for you.

Differences in sensory processing, executive functioning and having a lower number of spoons can add more layers of difficulty for neurodivergent folks experiencing these conditions. In my experience self-compassion, a healthy dose of rage at the system, community care and an understanding healthcare team can make all the difference.

Written by Sam Jeffrey (he/him), a neurodivergent (AuDHD) naturopath based on Whadjuk Noongar land and a proud queer, trans man. He is deeply committed to creating healthcare spaces where neurodivergent, queer and trans folks feel safe, respected and genuinely understood.

This article is intended as general advice only and does not replace medical advice. It is recommended that you seek personalised advice specific to your individual needs.