Ask a room of POTS specialists what causes it, and you’ll get more than one answer. That’s because there usually isn’t just one.
A 2026 review in Frontiers in Neurology describes POTS as a syndrome with one shared definition but multiple underlying drivers. For some people it starts after a virus. For others it follows a concussion, surgery, or seems to come out of nowhere. Here’s what researchers know so far.
Key Takeaways
- POTS has several overlapping causes, not one.
- Low blood volume, blood pooling, nerve changes, and excess adrenaline are the main mechanisms.
- Triggers include viral illness, surgery, concussion, and hormonal shifts.
- EDS, autoimmunity, and family history can raise risk.
What Happens Inside the Body Most cases involve one or more of these problems.
They often overlap.
Low Blood Volume
This is the most common finding. Cleveland Clinic Journal of Medicine reports that up to 70% of people with POTS have low blood volume.
The same review puts the average plasma volume deficit at about 13%. That’s roughly 650 milliliters, or about 2.5 cups, for a person with 5 liters of blood. With less blood to go around, the heart beats faster to keep your brain supplied when you stand. It’s also why doctors often recommend extra fluids and salt.
Blood Pooling in the Legs and Belly
Gravity pulls blood downward when you’re upright. Normally your blood vessels tighten to push it back up. In POTS, that doesn’t work well. Johns Hopkins Medicine lists excessive pooling of blood below the heart when upright as a key driver of symptoms.
Nerve Damage (Neuropathic POTS)
The nerves that tell your leg and belly vessels to tighten can be damaged. According to Cleveland Clinic Journal of Medicine, about half of patients with POTS have partial sympathetic denervation. In plain terms, the signal to tighten up gets weaker.
Too Much Adrenaline (Hyperadrenergic POTS)
Some people have high levels of stress hormones when upright. Hopkins notes that elevated epinephrine and norepinephrine contribute to symptoms in some patients. That can bring on tremor, sweating, and a pounding heart.
Deconditioning
After a long illness or injury, weeks in bed can leave your heart and leg muscles weaker. The Frontiers in Neurology review notes that relative low blood volume and physical deconditioning are common in POTS. This is one reason treatment often includes gradual exercise.
Common Triggers
Many people can point to a starting event. A recent review lists viral infection, hormonal changes like menarche, pregnancy, and perimenopause, adolescent growth spurts, physical trauma including concussion, and surgery as common triggers.
Picture a college student who gets the flu and spends a week in bed. When she finally gets up, her heart pounds every time she stands in line. Stories like this are common.
COVID-19
The pandemic put POTS in the spotlight. A 2026 meta-analysis found a pooled POTS prevalence of 36.2% among people with lingering post-COVID symptoms.
Why does it happen? Researchers aren’t sure. A late-2025 study says viral or immunemediated factors, along with prolonged bed rest and deconditioning, may all play a role.
Why Some People Never Find a Clear Cause
That’s common, and it isn’t your fault. Even researchers are still sorting out which findings are root causes. One 2026 review says it’s unclear whether these abnormalities are primary causes, downstream effects, or interacting contributors across patient groups.
Autoimmune Factors
The immune system may be involved in some cases. A 2025 review found that people with POTS have more non-specific autoimmune markers, including antinuclear antibodies, than the general population. The
Frontiers in Neurology review adds that a subset of patients have autoimmune conditions and, in some groups, circulating autoantibodies aimed at autonomic receptors. It’s an active research area, not a settled answer.
Connective Tissue and Overlapping Conditions
Ehlers-Danlos syndrome (EDS) affects the tissue that supports your joints and blood vessels. Looser vessel walls may let more blood pool.
The overlap is large. A 2026 systematic review found that nearly half of people with EDS also have POTS, and about one-quarter of those with POTS have EDS.
Hopkins also points to a link between POTS, joint hypermobility, and mast cell disorders. If you’re very flexible, bruise easily, or have frequent allergy-like reactions, tell your doctor.
Genetics and Family History
POTS can run in families. But Hopkins says no single gene explains most cases. A change in the norepinephrine transporter gene seems to affect only a tiny fraction of patients.
So if your mom or sister has it, your risk may be higher. It doesn’t mean you’ll get it. It’s just worth mentioning to your doctor.
What Doesn’t Cause POTS
Two common myths are worth clearing up.
Anxiety. Some symptoms overlap, but Dysautonomia International states that POTS is not caused by anxiety.
A heart defect. In most patients, the structure of the heart is normal. The heart is reacting to a circulation problem.
Who’s Most at Risk?
POTS hits women far more often than men, at about a 9-to-1 ratio, with onset typically between ages 12 and 50. Teens and young adults are the most common group. But men and older adults can get it too, so speak up if the symptoms fit.
What This Means for You
Knowing your likely drivers helps your doctor choose a plan. Before your appointment, write down any recent infection, injury, or surgery. Note joint problems and relatives with similar symptoms.
Questions worth asking:
- Could low blood volume be part of my POTS?
- Should I be checked for joint hypermobility?
- Did my recent illness or injury play a role?
Since blood pooling in the legs is part of the picture for many people, some look into nutritional circulation support. Real Science Nutrition’s Venous Miracle is designed to support healthy venous blood flow and everyday leg comfort. It isn’t a treatment for POTS, so check with your healthcare provider first.
Crux of the Matter
POTS rarely has one cause. Low blood volume, blood pooling, nerve changes, and excess adrenaline often work together, and triggers like infections or surgery can set them off. You may never pinpoint exactly why it started, and that’s okay. What matters is an accurate diagnosis and a plan that fits you.