Medical Disclaimer: The information provided here is for educational purposes only and is not a substitute for professional medical advice, diagnosis, or treatment. Do not start, stop, or change any treatment based on this information without consulting your doctor. Always seek personalized medical care to address your specific health concerns and conditions.
Postural Orthostatic Tachycardia Syndrome (POTS) a Type of Dysautonomia
Have you ever stood up too fast and felt lightheaded for a brief moment? This lightheadedness happens because gravity quickly pools blood in your lower extremities, momentarily reducing flow to your brain. However, your autonomic nervous system quickly corrects it by increasing heart rate and constricting blood vessels, so the dizziness fades in seconds.
A subset of patients with Postural Orthostatic Tachycardia Syndrome (POTS) have a much slower or insignificant constriction of blood vessels upon standing due to dysfunction of the autonomic nervous system (dysautonomia). Instead of reducing blood vessel diameter, the body attempts to maintain adequate blood pressure by increasing heart rate. Those who are not POTS experts tend to think that this mechanism, termed neuropathic POTS, is responsible for nearly all POTS cases. However, we will learn in this article that that is simply not true.
We sat down with Satish Raj, MD, one of the world’s leading POTS experts, to understand the various drivers of POTS and gain invaluable advice on ways to manage this medical condition. If you or a loved one has POTS and wants to learn about the science of this condition, then this article is for you. Let’s begin by understanding the function of the autonomic nervous system.
What is the Autonomic Nervous System?
The autonomic nervous system automatically regulates involuntary bodily functions essential for survival, such as heart rate, blood pressure, breathing, digestion, sweating, pupil dilation, and body temperature. All of these vital functions are achieved without conscious thought.
Dr. Raj explains that the brainstem largely controls the autonomic nervous system and should be described more accurately as the “automatic nervous system.” Borrowing from a colleague’s analogy, he compares it to the “Internet of Things, which is the idea that you can wire your house and have everything controlled, really, through this system. The fridge isn’t necessarily part of the autonomic nervous system; the lights aren’t, but the wiring that permeates every part of it is, and that’s sort of what the autonomic nervous system is.”
The Brain Inflammation Collaborative is on Substack!
The Physiology Explained: How and Why Do Blood Vessels Constrict When You Stand Up?
Neuropathic POTS is attributed to a partial failure of blood vessel constriction upon standing. Understanding what might be ‘broken’ in this subgroup of POTS patients starts with key basic concepts of blood pressure regulation when transitioning from lying or sitting to standing.
As discussed, your blood pressure briefly drops when you stand up. This drop in blood pressure is detected by tiny pressure sensors, called baroreceptors, in the walls of arteries in your neck and near your heart (image below, circle 1). The baroreceptors are specialized nerve cells that detect subtle changes in the stretch of a vessel wall. When the vessel’s stretch decreases, due to a drop in blood pressure when you stand upright, the nerve fires a signal to the brainstem (image below, circle 1). Here, the brainstem sends a signal back to the vessels (image below, circle 2), instructing the vascular smooth muscle cells that hug medium-sized blood vessels to constrict, narrowing the vessel diameter (image below, circle 3), and also signals the heart to increase the firing rate. This signal relay happens within seconds to keep blood flowing to your brain by maintaining a steady blood pressure.
Neuropathic Features in POTS
Dr. Raj explains that true damage to the autonomic nerves is relatively uncommon in POTS. In some patients, there can be actual nerve damage (autonomic failure), where “microscopically you may be able to look at ganglia and look at nerves, and there’s fallout” and “the nerve signals just don’t get through [to cause vasoconstriction].”
These patients typically present with orthostatic hypotension and loss of autonomic functions such as sweating. However, he stresses that most people with POTS do not have this kind of clear nerve damage. Instead, the autonomic nervous system often responds appropriately to underlying problems or can have an exaggerated response, rather than being broken and unable to respond on its own.
POTS Causes: Is A Dysregulated Nervous System Always to Blame?
Dr. Raj frequently cautions that “dysautonomia” is a broad, imprecise, and somewhat vague “grab-bag” term that encompasses a wide spectrum of issues ranging from clear-cut nerve damage to much subtler, harder-to-prove problems. Current testing often falls short of capturing or definitively proving these nuances. “The problem with dysautonomia as a label or as a diagnosis is that it’s hard to disprove. It’s hard to say there’s nothing wrong because many potential causes of POTS don’t have brilliant tests.” For example, in a subset of POTS cases, the autonomic nervous system may be responding appropriately to an underlying issue, such as low blood volume (hypovolemic POTS) or excessive sympathetic nerve firing (hyperadrenergic POTS), rather than being primarily dysfunctional itself.
Dr. Raj stresses that POTS is a syndrome (cluster of symptoms), not a single disease: “POTS isn’t one thing, it’s heterogeneous in terms of cause, there are different things that occur in different people in different proportions. The autonomic response (rapid heart rate) is often an appropriate compensatory response to these upstream triggers, not a primary dysfunction.” This concept shifts treatment toward addressing root issues (i.e., low blood volume) rather than assuming broken autonomic wiring.
"POTS isn't one thing, it’s heterogeneous in terms of cause, there are different things that occur in different people in different proportions. The autonomic response (rapid heart rate) is often an appropriate compensatory response to these upstream triggers, not a primary dysfunction."
Emerging Mechanisms: Rapid Heart Rate Due to Hyperventilation
Low levels of carbon dioxide dissolved in the blood after standing is emerging as an alternative mechanism to explain POTS. Dr. Raj explains that “low CO2 does cause the brain blood vessels to constrict and perhaps compromise the blood flow [to the brain]”. It can also cause peripheral blood vessels to vasodilate. Together, these may play a role in the rapid increase in heart rate that defines POTS.
This explanation might seem counterintuitive when comparing it to neuropathic POTS. But let’s assume for a moment that a person has proper blood pressure regulation upon standing, yet still has a rapid heart rate. The increased heart rate might be due to CO₂. Here is how.
Carbon dioxide is a powerful regulator of cerebral blood vessel diameter. Higher CO₂ levels in the blood cause vessel dilation (opening wider), while lower CO₂ levels cause vessel constriction (narrowing). Therefore, exhaling too much CO₂ can reduce cerebral blood flow (hypoperfusion), even when systemic blood pressure is relatively preserved. The brain senses this drop in blood flow and thus in oxygen delivery, and compensates by increasing heart rate to restore adequate oxygen delivery to the brain.
Postural Hyperventilation in a Subgroup of POTS Patients
Dr. Raj points out that there is a recognizable subgroup of POTS patients who hyperventilate (breathe off too much CO₂), specifically when they move from lying down to standing. This pattern is called postural hyperventilation.
“Years ago, Julian Stewart did some nice studies and coined the phrase postural hyperventilation to describe a subgroup of patients with POTS. When they stood up, they were hyperventilating more, and that may have been contributing to their tachycardia and related symptoms.” So in these patients, the simple act of standing triggers faster or deeper breathing, which lowers CO₂ and may help drive the excessive heart-rate response.
Dr. Raj’s Research on CO₂ and POTS
Dr. Raj’s lab has been actively studying this phenomenon using a technique called gas clamping, which precisely controls and measures how CO₂ levels affect the body. Their findings show that, while the mechanical act of breathing itself plays only a small role, “the CO2 and the posture outside of ventilation still play a significant role in the heart rate increase”.
He and his team are now asking whether preventing that CO₂ drop could become a practical treatment. “It sort of raises the issue as to whether that can be used as a treatment. If you actually can prevent the CO2 from falling too much, will that actually help blunt the tachycardia?”
The equipment they use in the lab is large and expensive, so they are looking for simpler, more practical ways that patients might eventually use at home. “These machines aren’t things you take home with you. The machine that we used to restore the CO₂ costs $100,000 and is the size of a refrigerator, so our next phase is to try and look at more practical approaches to manipulating CO₂.”
Bottom line for patients: If you’ve noticed that your breathing feels different or faster when you stand and your heart races more than usual, you may be in the subgroup Dr. Raj is studying. His team is actively exploring whether helping keep CO₂ levels steadier could one day become a helpful tool for managing POTS symptoms. It’s important to note that this is still research in progress and is not something to try on your own yet. However, it offers another piece of the POTS puzzle and reason for hope that more targeted options may be coming.
How To Diagnose POTS: A General Consensus
To receive a formal diagnosis, all of the following must typically be met (adapted from current consensus, including the 2020 Canadian Cardiovascular Society and a 2019 panel of POTS experts position statement and ongoing 2026 updates):
- Sustained orthostatic tachycardia:
- Heart rate increase of ≥30 bpm from supine (lying down) to upright position within the first 10 minutes of standing or head-up tilt (for adults aged 20+).
- For adolescents (aged 12–19 years): ≥40 bpm increase (higher threshold due to normal physiologic responses in younger people).
- Absence of significant orthostatic hypotension:
- No drop in systolic blood pressure of ≥20 mmHg or diastolic ≥10 mmHg within the first 3 minutes of standing (this distinguishes POTS from classic orthostatic hypotension).
- Chronic symptoms of orthostatic intolerance:
- Symptoms must be present for at least 3 months (in many guidelines) and worsen when upright, with rapid improvement (or relief) upon returning to a supine (lying down) position.
- Common symptoms include lightheadedness, brain fog, fatigue, palpitations, tremulousness, blurred vision, nausea, shortness of breath, and exercise intolerance (as discussed in prior responses).
- No other overt cause:
- Symptoms and tachycardia are not better explained by acute dehydration, blood loss, medications, anemia, hyperthyroidism, or other conditions that mimic POTS.
These criteria focus on presentation rather than etiology (underlying cause), as POTS is heterogeneous.
Tilt Table Test
The tilt table test is a non-invasive diagnostic procedure commonly considered the gold standard for confirming Postural Orthostatic Tachycardia Syndrome (POTS) and other forms of orthostatic intolerance or autonomic dysfunction. It simulates the gravitational effects of standing while allowing precise, continuous monitoring of your heart rate, blood pressure, and symptoms in a controlled environment.
The test evaluates how your autonomic nervous system responds to a change from lying flat (supine) to an upright position. In POTS, the key finding is a significant increase in heart rate (≥30 bpm in adults, or ≥40 bpm in adolescents) within 10 minutes of tilting, without a major drop in blood pressure (which would indicate orthostatic hypotension instead). It helps reproduce symptoms such as lightheadedness, brain fog, or palpitations safely while ruling out other causes (e.g., arrhythmias or structural heart issues).
POTS Symptoms
Common POTS symptoms include lightheadedness, palpitations, exercise intolerance, and brain fog, symptoms that “are fairly proletarian… we all get,” but become severe and contextual in POTS.
Orthostatic (Upright-Triggered) Symptoms
These tend to flare or intensify when standing, sitting upright for long periods, or during prolonged activity:
- Lightheadedness— Often described as feeling like you’re about to faint; very common (nearly universal in many reports).
- Brain fog — Difficulty concentrating, memory lapses, slow thinking, feeling “mentally cloudy” or detached.
- Fatigue/exhaustion — Profound tiredness that doesn’t fully resolve with rest; one of the most draining and persistent complaints.
- Palpitations or forceful heartbeats — Awareness of pounding, skipping, or racing heart (beyond just the measured rate increase).
- Shortness of breath (dyspnea) — Feeling like you can’t get enough air, even without exertion.
- Tremulousness/shakiness — Trembling or internal trembling, especially in hyperadrenergic subtypes.
- Blurred or tunnel vision — Visual changes due to reduced brain blood flow.
- Headaches (including migraines) — Frequent or severe, often worsening upright.
- Nausea — Can range from mild queasiness to vomiting.
- Generalized weakness — Legs feeling heavy, “rubbery,” or like they might give out.
- Chest discomfort/pain — Pressure or tightness, sometimes mimicking heart issues.
- Acrocyanosis — Reddish-purple discoloration or mottling of hands/feet/legs from blood pooling.
Non-Orthostatic / Generalized Symptoms
These can occur even when lying down or sitting, contributing to overall chronic burden:
- Chronic fatigue — Persistent, overwhelming tiredness (often compared to chronic fatigue syndrome overlap).
- Sleep disturbances — Trouble falling asleep, staying asleep, unrefreshing sleep, or excessive daytime sleepiness.
- Gastrointestinal issues — Nausea, bloating, abdominal pain, early satiety, irritable bowel-like symptoms, gastroparesis (slow stomach emptying), or rapid gastric emptying.
- Exercise intolerance — Symptoms dramatically worsen after even mild activity; post-exertional malaise is common.
- Temperature dysregulation — Excessive sweating, feeling too hot/cold, or poor temperature control.
- Pain syndromes — Widespread chronic pain, joint hypermobility-related aches (especially in Ehlers-Danlos syndrome overlap), or neuropathic sensations.
- Cognitive and mood effects — Anxiety-like feelings (from physiological adrenaline surges), depression secondary to chronic illness, or sensory overload.
These symptoms vary widely between individuals. Some have mostly orthostatic issues, while others deal with orthostatic symptoms in addition to generalized symptoms.
Patients with POTS can also present with numerous comorbidities, such as connective tissue disorders like Ehlers-Danlos syndrome (EDS), mast cell activation syndrome (MCAS), and infection-associated chronic conditions like Long COVID and post-infectious ME/CFS.
Non-Pharmacological POTS Treatments
When it comes to treating Postural Orthostatic Tachycardia Syndrome (POTS), Dr. Satish Raj focuses on practical strategies that target one of the most common underlying issues he sees: low blood volume (hypovolemia). He explains that many people with POTS have reduced stroke volume when standing, meaning the heart pumps out less blood with each beat. Reduced blood volume could lead to reduced oxygen delivery to the brain. The body tries to prevent this inadequate oxygen delivery to the brain by forcing the heart to beat faster.
One of the main treatment strategies Dr. Raj highlights is increasing blood volume through higher salt and fluid intake. “We think a lot of the problem is that their stroke volume drops, part of what drives the heart rate is probably not enough blood getting back to the heart, and that’s sort of part of our strategies for treatment, which is increasing blood volume.”
Dr. Raj shared results from a study he conducted at Vanderbilt in which patients followed a low-sodium diet for a week, then a high-sodium diet for a week, in random order. The high-sodium phase improved plasma volume and led to meaningful changes: “When we went to the high sodium diet, we improved their plasma volume, their orthostatic tachycardia did go down, their upright plasma norepinephrine levels did go down, and their symptoms did seem to get better.”
He notes that increasing blood volume helps many patients with lightheadedness and palpitations, though it may not completely resolve every symptom (such as migraines or gut issues). “If we’re talking about symptoms of lightheadedness and palpitation and those things, does it make it better? I think the answer is yes.”
The key takeaway is that treatment should focus on addressing the underlying contributors (such as low blood volume, low blood CO2, or excessive sympathetic nerve activation) rather than just bemoaning that the autonomic nervous system itself is broken. Volume expansion through salt and fluids is one of the practical, first-line approaches he highlights in patient discussions.
Living with POTS: A Message of Hope from Dr. Raj
If you’re feeling discouraged or overlooked in your POTS journey, Dr. Satish Raj offers genuine reasons for optimism. “The fact that there’s this [industry] interest [in POTS] is a positive step,” he says. Recognition of POTS has grown dramatically in the last decade, especially with the attention brought by Long COVID, where a POTS-like presentation appears in many patients. “What has changed is recognition. There are people actually then saying, okay, well, I have this drug, maybe it could be useful for POTS”.
Dr. Raj explains that POTS is on the radar of pharmaceutical companies and device makers, leading to clinical trials, new drug candidates in phase 2 studies, wearable monitoring tools, and research into treatments such as vagal nerve stimulation. While Dr. Raj acknowledges that drug development takes time and there won’t be a quick fix tomorrow, he encourages patients to hold on: “Hopefully, if we look out a decade from now, or maybe a bit longer, we’re going to start to reap the fruits.”
Written By
Matthew Menendez, Ph.D.
Director of Science Communication, Brain Inflammation Collaborative
Dr. Menendez has a passion for empowering patients navigating complex chronic diseases. Through innovative educational strategies, he bridges the gap between cutting-edge research and real-world understanding, helping individuals advocate for better care, access timely treatments, and reclaim their quality of life.
