Understanding the EDS, MCAS, POTS Connection
EDS, MCAS, POTS:
Understanding Your Body’s Energy Crisis
Your Body’s Hidden Struggle
If you’re living with Ehlers-Danlos Syndrome (EDS), Mast Cell Activation Syndrome (MCAS), and Postural Orthostatic Tachycardia Syndrome (POTS)—often called the evil triad—you know how these conditions intertwine. A flare in one, like joint pain, allergic reactions, or dizziness, often sets off a chain reaction, making everything feel worse. These conditions aren’t separate; they’re deeply connected, like a web where a tug on one thread affects the whole. At the heart of this web is your body’s energy system, struggling to keep up.
This page is here to help you understand why these conditions happen together and how your body’s cellular energy production—bioenergetics—plays a central role. By seeing the bigger picture, you can start to find a path toward healing.
(Clinicians: For a detailed explanation, please read our Mechanistic Model of EDS/MCAS/POTS)
What Sets This Cycle in Motion?
Your body is like a finely tuned machine, but certain events can throw it off balance, especially if you're genetically predisposed (e.g., variations in tissue-building genes). These events don’t cause these conditions directly; instead, they act as the proverbial “straw that breaks the camel’s back”, amplifying stress or kicking off a vicious cycle on an already vulnerable system, setting off a cascade affecting everything from joints to immunity.
Common triggers include:
Infections, including COVID-19: These can initiate or intensify long-lasting inflammation, destabilizing mitochondrial and immune function.
Medical stressors, especially COVID vaccines: For some, these can tip an already stressed system into full-blown dysregulation.
Chronic stress: Emotional or physical strain draining your reserves.
Physical injuries: Concussions, whiplash, or trauma, especially to the head or neck.
Hormonal shifts: Puberty, pregnancy, or menopause altering your body’s balance.
The Energy Crisis: Why Your Cells Are Struggling
At the core of EDS, MCAS, and POTS is a problem with your mitochondria, the tiny energy factories in your cells. They create the energy needed to repair tissues, regulate immunity and protein function, reduce inflammation and much more. When stressed, mitochondria produce insufficient energy and release harmful byproducts called reactive oxygen species (ROS), which leads to oxidative stress and can damage cells, much like rust on metal.
Environmental factors stress your mitochondria, as discussed below, creating a vicious cycle that fuels EDS, MCAS, and POTS.
Why MCAS Is Often the First to Show Itself
As the mitochondria become increasingly stressed, mast cells—key immune system defenders—become hypersensitive, releasing histamines in response to a growing range of triggers. Histamine, a chemical messenger, drives allergic reactions leading to symptoms like itching, swelling, rashes, or digestive distress, and amplifies inflammation throughout the body.
Mast cells don’t just cause allergic reactions, though, they also:
Weaken protective barriers: Release enzymes, such as elastase and tryptase, that loosen the tight connections in your gut lining, blood-brain barrier, and blood vessels. This increased permeability allows unwanted substances to leak through, causing inflammation.
Alter tissue growth: Produce growth factors, like TGF-Beta and VEGF, that prompt the body to remodel tissues. This can weaken structural stability and lead to abnormal blood vessel growth.
Damage connective tissue: Disrupt the formation of collagen and the fascial system, the scaffolding that supports your body. This results in loose joints, fragile connective tissue, and slower wound healing.
Irritate nerves: Release chemicals that activate nearby nerves, increasing pain sensitivity and inflammation in a process called neurogenic inflammation.
Over time, mast cell hyperactivity reshapes connective tissue integrity. In non-genetic hypermobile forms of EDS, this is likely the root cause of joint laxity and fascia instability. Emerging evidence suggests MCAS—driven by mitochondrial collapse due to environmental stress—may precede EDS in many cases.
How It All Connects: The Vicious Cycle
Here’s how this cellular energy crisis links the three conditions:
Tissue Weakness (EDS): Weakened mitochondria produce less energy and release harmful byproducts called reactive oxygen species (ROS), which, along with mast cell chemicals, damage collagen. This leads to overly flexible joints and weakened fascia. Connective tissues—like ligaments, tendons, and fascia—rely on healthy mitochondria to stay strong. When they weaken, they cause joint instability, partial dislocations, and even spinal problems, such as craniocervical instability (where the skull and neck misalign), which can disrupt your nervous system.
Barrier Breakdown: When mitochondria produce less energy, they weaken the tight junctions—protein "zippers" that seal the gut lining, blood-brain barrier, and blood vessels. This leads to leaky gut, a leaky blood-brain barrier, and fragile blood vessels. As these barriers become permeable, toxins, food particles, and immune triggers slip into the bloodstream. This not only causes inflammation in the gut and brain but also disrupts immune balance and nervous system signaling.
Immune Hyperreactivity (MCAS): Leaky barriers allow toxins, food particles, and other triggers to slip into the bloodstream, intensifying chronic mast cell activation. This heightened response further weakens barriers, as the activated mast cells disrupt tight junctions in the gut, blood-brain barrier, and blood vessels. The result is a self-reinforcing cycle where increased barrier permeability drives more mast cell activity, amplifying immune and nervous system responses and making recovery after triggers more difficult.
Nervous System Dysregulation: Before blood flow issues arise, the nervous system starts to malfunction. Stress on mitochondria, weakened connective tissues, and overactive immune responses trigger a "cell danger response," a protective state where cells prioritize survival over normal function. This disrupts brainstem and vagus nerve pathways, which control heart rate, digestion, and relaxation, pushing the body into a constant "fight-or-flight" mode.
Limbic System Amplification: The limbic system, the brain’s emotional center, can worsen and sustain this dysfunction. Chronic stress or trauma heightens its sensitivity, making it perceive threats even in neutral situations. This overactive limbic system fuels mast cell activation, destabilizes autonomic functions (like heart rate and blood pressure), and intensifies immune responses. Connected to the hypothalamus and brainstem, it influences fear, pain, and inflammation. When stuck in hypervigilance, it triggers full-body reactions to minor stimuli, reinforcing the cycle of dysregulation.
Circulatory Instability (POTS): Nervous system stress disrupts baroreceptors—sensors in your arteries that monitor blood pressure—causing them to misread pressure changes. This impairs the blood vessels’ ability to constrict properly. Combined with loose connective tissues from EDS, this leads to blood pooling in the legs when standing. To compensate, the heart races, causing dizziness, fatigue, palpitations, or fainting—key symptoms of POTS.
Dysautonomia: POTS is one type of dysautonomia, a condition where the autonomic nervous system—which controls automatic functions like heart rate, digestion, and temperature—starts to malfunction. Other symptoms include irregular digestion, unstable body temperature, chronic anxiety, dilated pupils, and fluctuating blood pressure. As upstream systems like mitochondria, tissues, and immunity destabilize, the brainstem struggles to regulate the body’s autopilot, making once-automatic functions unpredictable and exhausting.
This self-reinforcing cycle drives EDS, MCAS, and POTS: weakened tissues spark inflammation, overactivating the immune system, which disrupts nerves and blood flow, further damaging tissues. Struggling mitochondria and harmful reactive oxygen species (ROS) impair the body’s ability to recover, perpetuating symptoms like pain, fatigue, and dizziness.
Modern Life Fuels the Fire
Our environment doesn’t make it easier. Beyond the triggers above, everyday factors keep this cycle going:
Lack of sunlight: Natural light optimizes mitochondrial function and regulates histamine, melatonin, and immunity, but most lack sufficient exposure.
Artificial light: Blue light from screens/LEDs, especially after dark, disrupts energy production, circadian rhythms, and mitochondrial repair.
Electromagnetic fields (EMFs): WiFi, Bluetooth, and cell signals may trigger mast cell degranulation and degrade mitochondrial function.
Toxins: Chemicals in food, water, or air add cellular strain.
Chronic stress: Ongoing pressure keeps the body in sympathetic overdrive, impairing tissue repair and barriers.
Post-viral and post-vaccine stress: Viral infections like COVID-19—and their vaccines—can intensify inflammation and mitochondrial stress, especially in sensitive individuals. Elements such as spike protein and lipid nanoparticles (LNPs) may further disrupt immune signaling and tissue repair.
Dehydration and low minerals: Without mineral-rich water, cells lose charge and barrier integrity.
Processed foods: Nutrient-poor foods lack minerals and cofactors for energy and tissue resilience.
These factors directly harm your body’s ability to produce energy, regulate immunity, and heal from within.
Long COVID and the Triad
Long COVID shares striking similarities with EDS, MCAS, and POTS, amplifying the same cycle of dysfunction. Symptoms like fatigue, brain fog, dizziness when standing, food sensitivities, and unstable body temperature mirror the triad’s hallmarks. For many, Long COVID may not be a new illness but an unmasking of underlying issues—mitochondrial stress, leaky barriers, overactive mast cells, and autonomic nervous system imbalances. COVID-19 acts as a powerful trigger, intensifying these weaknesses alongside modern environmental stressors, pushing the body deeper into the self-reinforcing cycle described above.
Breaking the Cycle: A Path to Healing
Understanding this cycle offers multiple healing strategies. Instead of masking symptoms, support your body’s energy system and resilience:
Restore mitochondrial health for adequate energy.
Reduce environmental stress to enhance cellular recovery.
Strengthen protective barriers to reduce inflammation.
Bolster tissue stability for structural integrity.
Soothe immune responses to minimize hypersensitivity.
Calm the nervous system to restore balance.
Optimize nutrient use to support energy and repair.
Your Body’s Resilience
Your symptoms aren’t the illness, they’re your body’s attempt to cope with an overwhelming environment. EDS, MCAS, and POTS signal your body’s protective efforts. With support, it can heal remarkably.
This journey requires time and often a team, functional medicine doctors, physical therapists, nutritionists, and educators like myself. I’ve walked this path and know it’s challenging. Focusing on your body’s energy system and root causes can help you feel stronger and balanced.
Moving Forward
Healing from EDS, MCAS, and POTS is about restoring your body’s ability to adapt and thrive. Small changes such too your environment, along with better hydration, whole foods accumulate over time. You’re not alone, and improvement is possible with patience and the right approach.
Note: This information is for education only and isn’t a substitute for medical advice. Always work with healthcare providers experienced in EDS, MCAS, and POTS to create a personalized plan.