Postural orthostatic tachycardia syndrome (POTS) is often described by a rapid heart rate and dizziness upon standing. But that does not describe the full impact of POTS or what causes it. POTS is a multisystem disorder of the autonomic nervous system involving cardiovascular, neurological, immune, and endocrine abnormalities.
In my patients, POTS is rarely a stand-alone diagnosis. It is a downstream effect of chronic infections, environmental toxins, immune dysregulation, mast cell activation, and mitochondrial damage. This article reviews the research on the drivers of POTS and why lasting recovery requires treating the underlying causes.
What is POTS?
The autonomic nervous system regulates the functions we do not consciously control — heart rate, blood pressure, digestion, and temperature. When a person stands, gravity pulls roughly a liter of blood toward the lower body. A healthy autonomic nervous system responds instantly, tightening blood vessels to keep blood flowing to the brain. In POTS, that response fails, and the heart compensates by racing.
POTS is characterized by an increase in heart rate of at least 30 beats per minute (40 in adolescents) within 10 minutes of standing, without a drop in blood pressure. It predominantly affects women, and the typical onset is between ages 15-50.
POTS is not a heart issue. The heart is responding to other mechanisms that cause blood to pool in the lower body
POTS is Not One Condition
Like other complex conditions, POTS is heterogeneous. Patients fall into overlapping subtypes:
- Neuropathic POTS — dysfunction or damage of the small autonomic nerves that control blood vessel tone. This commonly presents with blood pooling in lower extremities and cold hands and feet. This is the most common pattern I see in complex chronic illness.
- Hyperadrenergic POTS — excessive norepinephrine, producing tremor, sweating, elevated blood pressure, and adrenaline surges causing anxiety and insomnia.
- Hypovolemic POTS — reduced blood volume and impaired volume regulation. A person may experience excessive thirst, salt craving, and low blood pressure.
Most patients have features of more than one. Deconditioning is often layered on top, but in my experience it heightens POTS rather than causes it. Treating deconditioning as the diagnosis is one of the most common reasons patients fail to improve.
Chronic Infections Drive POTS
The onset of POTS typically develops following a trigger. I commonly see POTS triggered in people after a chronic infection.
There is a strong relationship with POTS and Long COVID. In a study of 467 highly symptomatic long COVID patients, 31% met the diagnostic criteria for POTS.1 Before the pandemic, POTS affected well under 1% of the population. POTS has also developed in people following the mRNA COVID vaccine.2 Epstein-Barr virus and other viral illnesses have long been recognized as triggers.
Tick-borne infections are a frequently overlooked cause of POTS. One study described patients who had been successfully treated for classic Lyme symptoms, only to develop fatigue, cognitive dysfunction, and orthostatic palpitations later when they were diagnosed with POTS.3 More recent research has confirmed that autonomic dysfunction is a key component of persistent symptoms following Lyme disease.4 In my practice, Bartonella and Babesia frequently contribute to the immune dysregulation that destabilizes the autonomic nervous system.
When POTS begins after an infection, the infection is not incidental. It is the place to look.
Mold and Mycotoxins Contribute to POTS
Molds produced in water-damaged buildings release mycotoxins that cause oxidative stress, immune dysregulation, and neurological damage, the same mechanisms of injury that impair autonomic function.
In a large case series of patients exposed to mold and mycotoxins, objective autonomic nervous system testing was abnormal in nearly all patients tested, with the most common abnormalities involving heart rate.5 Mycotoxins are established neurotoxins that cross the blood-brain barrier, activate the brain’s immune cells, and trigger the neuroinflammation that disrupts the brainstem regions responsible for regulating heart rate and blood pressure.
In the patients I see, toxin burden is often overlooked as a contributor to POTS/dyautonomia. I have treated patients whose POTS was solely caused by mold-related illness. Elevated mycotoxins should be tested for in anyone with POTS and a suspected history of mold exposure.
POTS and Mast Cell Activation Syndrome
Of all the conditions that overlap with POTS, none is more strongly associated than mast cell activation syndrome (MCAS). Mast cells are immune cells that are in high concentrations in tissue that interface with the environment – skin, respiratory, and gastrointestinal tracts. When chronically overactive, mast cells release histamine and other mediators that are potent vasodilators. Those mediators dilate blood vessels and cause blood to pool in the lower body, reducing venous return and resulting in POTS symptoms. A significant subset of people with POTS/dysautonomia have mast cell activation as the driver, a connection first described two decades ago.6
MCAS is characterized by episodic flushing, allergic-like reactions, hives, food or chemical sensitivities, unexplained GI symptoms, or flares triggered by alcohol and heat. How often the two co-occur is difficult to determine, but prevalence can be high depending on the diagnostic criteria used.7 Addressing MCAS by avoiding triggers, using antihistamines, and mast cell stabilizers improves outcomes in POTS treatment. Stress, limbic injury, and cell danger response can also play a role in mast cell reactivity.
Mitochondrial Dysfunction and POTS
Mitochondria are known as the powerhouses of the cell, responsible for producing the energy for every function in the body, but they do much more. Maintaining blood pressure and heart rate against gravity is metabolically demanding work for the heart, blood vessels, and autonomic nerves. When the mitochondria do not generate sufficient energy, this system fails.
Mitochondrial dysfunction is always involved in complex chronic illnesses
In patients with confirmed mitochondrial disease, orthostatic intolerance and POTS occur at high rates.8 Therefore, improving mitochondrial function, when indicated, improves dysautonomia. This is also where the drivers of POTS converge. The same chronic infections and mold toxicity discussed above generate the oxidative stress that damages mitochondria, a primary reason POTS and chronic fatigue syndrome frequently occur together.
Autoimmunity and Nutrient Deficiencies
There is evidence that POTS has an autoimmune basis in some patients. Researchers have identified autoantibodies against adrenergic receptors – receptors that regulate blood vessel constriction and heart rate- in patients with POTS. These autoantibodies interfere with normal vascular constriction and drive an elevation in heart rate.9 Antibodies against acetylcholine receptors have been found in 29% of POTS patients in one cohort.10 POTS also overlaps with other autoimmune conditions including Sjögren’s, celiac, and thyroid disease.
Nutrient deficiencies are common and correctable contributors. Adolescents with POTS have lower iron stores than their healthy peers,11 and iron insufficiency along with low vitamin D has been documented in young patients with orthostatic intolerance.12 Vitamin B12, essential for healthy nerve function, is also frequently low. These deficiencies are worth looking into in every person, because they are simple to fix and can reduce symptoms.
The Symptoms of POTS
Because the autonomic nervous system regulates the entire body, the symptoms of POTS extend far beyond a fast heart rate.
- Cardiovascular — palpitations, a racing heart on standing, chest discomfort, and venous pooling
- Reduced blood flow to the brain — lightheadedness, fainting, brain fog, anxiety, depression, and visual greying
- Respiratory — shortness of breath, air hunger, frequent yawning
- Digestive — nausea, bloating, early fullness, constipation, and slowed motility
- Temperature — heat intolerance and abnormal sweating
- Gynecological – Pelvic pain, heavy periods
- General — fatigue, exercise intolerance, headaches/migraines, tremor, disrupted sleep, and “coat-hanger” pain across the neck and shoulders
For example, people with POTS may feel fine walking through an airport, but they feel faint when standing still in line. Instinctively, they cross their legs, shift their weight, or lean against something to increase blood flow back to their heart and brain.
The hallmark pattern is positional. Symptoms worsen when upright and after meals, improve when lying down, and are often worst in the morning. When I see a patient with POTS who experiences brain fog and anxiety, I let them know these are likely symptoms of reduced blood flow to the brain.
Conditions Associated With POTS
In addition to the illnesses that can lead to POTS listed above, other conditions are intertwined with POTS. Hypermobile Ehlers-Danlos syndrome (hEDS) is linked to POTS due to increased connective tissue laxity and is illustrated in the POTS/MCAS/hEDS cluster.13 POTS also clusters with hypercoagulation, small fiber neuropathy, gastroparesis (constipation), and migraines. These conditions travel alongside POTS and are worth exploring.
Lower Venous Insufficiency
Because gravity pulls blood downward, structural problems with the veins can worsen POTS. In one study, 69% of POTS patients had significant compression of the left common iliac vein compared with 40% of healthy controls.14 This condition is called May-Thurner syndrome and causes blood to pool in the legs, contributing to swollen feet and ankles, throbbing or aching in legs, pain that worsens with standing, and pelvic and lower back pain.
In a recent series, 83% of people diagnosed with POTS had confirmed iliac vein compression or pelvic venous congestion on imaging. Patients who underwent stenting of the compressed vein showed significant improvement in orthostatic symptoms.15 Venous pathologies are identified by an interventional radiologist with expertise in venous pathologies. The lead author of the linked study is a leading expert.
Diagnosing POTS
The diagnosis of POTS is confirmed by measuring the heart rate response to standing. The NASA Lean Test is a standardized exam that can be performed in the office or at home. Stand testing has been shown to be equivalent to or superior to the more involved tilt-table test. Because the NASA Lean Test is simple and repeatable, I use it for diagnosis and to track a patient’s response to treatment over time.
How to perform a NASA Lean test:
- Lie down quietly for 5 minutes and then take your heart rate and blood pressure
- Then stand and lean your upper back against a wall, with your feet shoulder-width apart and 6 inches from the wall.
- Do not cross arms, legs, or wiggle around while standing
- Record your blood pressure, heart rate, and any symptoms each minute for 10 minutes
- A rise in >30 beats per minute in an adult (>40BPM in an adolescent) is diagnostic of POTS. A decline of >10 mmHg diastolic or> 20 mmHg systolic within 3 minutes of standing is orthostatic hypotension
Since POTS usually results from an underlying cause that drives chronic inflammation and immune dysregulation, I order lab tests for underlying chronic infections and environmental toxins.
A Systems-Based Approach to Treatment
Recovering from POTS is a sequence, and the order matters. I begin by addressing POTS to stabilize the patient before beginning to treat the drivers of POTS. This improves symptoms associated with hemodynamic instability and enables further treatment for the drivers.
Lifestyle
POTS treatment starts with lifestyle support before or alongside introducing medication. The foundation is 2 to 3 liters of fluid and 6 to 10 grams of sodium daily, which expand plasma volume, improve venous return, and increase stroke volume. Waist-high or abdominal compression adds to this by reducing the venous pooling that drives the tachycardia, and it works far more effectively than calf-high compression alone.16
Medications
When medication is needed, the patient’s type of POTS can guide the choice of medication.
- Fludrocortisone — a synthetic mineralocorticoid that promotes sodium and water retention to expand plasma volume. Most useful in the hypovolemic subtype and in people with low blood pressure.
- Midodrine — constricts blood vessels to improve venous return and cerebral perfusion. Best suited to neuropathic POTS with prominent venous pooling.
- Pyridostigmine — an acetylcholinesterase inhibitor that improves autonomic balance and lowers standing heart rate. Helpful in hyperadrenergic POTS, in patients who don’t tolerate vasoconstrictors, and in those with digestive motility issues.
- Beta blockers such as propranolol — blunt the excess adrenaline of the hyperadrenergic subtype and slow the heart rate.
- Ivabradine — slows the heart rate directly, without lowering blood pressure. Particularly useful when rapid heart rate is prominent, blood pressure is already low, or beta blockers are poorly tolerated.
Once the patient is stable, I treat the underlying drivers. That means treating the chronic infections that triggered the illness, reducing mold and heavy-metal burden, calming mast cell activation, and correcting deficiencies such as iron and B12. Because the mitochondria sit downstream of each of these insults, I support mitochondrial and cellular healing. As the underlying causes are effectively treated, POTS can often be reduced.
POTS is More Than a Heart Rate Problem
As the research demonstrates, POTS results from multiple mechanisms of injury, including chronic infections, toxin exposure, immune dysregulation, mast cell activation, and mitochondrial dysfunction, all of which affect the autonomic nervous system. POTS is one of the most frequently overlooked pieces of the complex chronic illness picture. Patients spend years being told their racing heart, brain fog, and fatigue are anxiety or deconditioning, while a measurable, treatable condition is causing these symptoms.
POTS is one presentation of dysautonomia, and it affects the entire body, often co-occurs with conditions like MCAS, and is almost always a signal of something deeper. Recovering from POTS requires more than managing heart rate. It requires identifying and treating the underlying causes.
