~ POTS (postural orthostatic tachycardia syndrome) is a problem with how your autonomic nervous system regulates heart rate, causing it to increase suddenly when standing.
~ There are several different triggers or causes for POTS.
~ Genetic variants can make you more susceptible to the condition, and understanding your genes can help you target the right therapy.
Members will see their genotype report below, plus additional solutions in the Lifehacks section. Consider joining today.
Postural Orthostatic Tachycardia Syndrome (POTS): Background Science, Dysautonomia
Do you feel lightheaded when you stand? Does your heart suddenly race? POTS (postural orthostatic tachycardia syndrome) is a problem with how your autonomic nervous system regulates heart rate. POTS can also cause fatigue, brain fog, shaking, and other symptoms, in addition to lightheadedness when standing up.
Doctors define POTS as:
- an increase in heart rate of 30 BPM (beats per minute) within the first 10 minutes of standing
- Or an increase in heart rate to over 120 BMP within the first 10 minutes of standing[ref]
These requirements define POTS as long as the person doesn’t have orthostatic hypotension (a condition where blood pressure initially drops when standing).
For teens and kids, most doctors now define POTS as a heart rate increase of over 40 BPM.
Millions of people around the world have POTS. The Dysautonomia International website explains that POTS impacts 1 to 3 million Americans.
POTS Symptom Checklist:
✓ headaches, brain fog
✓ lightheaded, fainting, vertigo
✓ heart palpitations, chest pain
✓ exercise intolerance
✓ shaking, cold hands and feet
✓ abdominal pain, nausea, bloating
✓ diarrhea, constipation, bladder problems
Cause of POTS (Postural Orthostatic Tachycardia Syndrome):
POTS is a syndrome – meaning a collection of symptoms – rather than a specific disease. Thus there are a variety of diseases or chronic conditions that can cause POTS symptoms.
Diseases and conditions linked to triggering POTS include:
- Autoimmune activation of the adrenergic system[ref][ref]
- Autoimmune activation of the angiotensin II type 1 receptor[ref]
- Mast cell activation[ref]
- Viral illness, infections[ref]
- Joint hypermobility (found in about 50% of teens with POTS), Ehlers-Danlos[ref][ref]
- linked to the HPV vaccine (more studies are needed on this to show causality)[ref]
- Surgery, bed rest[ref]
- Inflammatory disorders[ref]
POTS is often made worse by heat stress.
From lying down to standing up: blood pressure and heart rate
When someone who does not have POTS gets out of bed and stands up, the body goes through a series of regulatory changes that alter heart rate. Because blood pressure and heart rate regulation are automatic, we aren’t even aware that they are taking place.
Upon standing, gravity causes blood to go from the chest to the lower abdomen and legs. Within the first 30 seconds of standing, there is a fluid shift between the blood vessels and the space in between the cells.
This change in blood volume causes receptors in the heart to be activated and alters the heart’s stroke volume.
All of this causes the heart rate to increase just a little bit normally. It also alters blood pressure slightly (decreased systolic BP, increased diastolic BP).[ref]
Thus, when standing up, a slight increase in heart rate and BP is normal.
What happens when a person with POTS stands up?
There are a couple of different scenarios of what is happening in people with POTS (more details below). But generally, POTS can be caused by low blood volume or by the blood vessels in the legs not constricting enough.[ref]
If the person with POTS is hypovolemic – reduced blood volume – they usually have an elevated heart rate even when at rest. This heart rate elevation worsens upon sitting or standing, and the heart rate increases substantially.
For someone with reduced vasoconstriction in the legs, the heart rate increases dramatically to maintain normal blood pressure. This increase could be worsened in high-heat conditions, causing more blood to flow to the skin.[ref]
Autonomic nervous system, blood regulation:
Dysautonomia is a term you will often see when reading about POTS. Essentially, dysautonomia means a dysfunction of the autonomic nervous system. It is a catch-all term, with several chronic conditions falling under the umbrella of dysautonomia.[ref]
The autonomic nervous system controls involuntary functions in the body – including heart rate, blood pressure, and the motility of the digestive tract.
The body tightly regulates blood pressure through the renin-angiotensin-aldosterone system. It balances out the volume of blood by regulating sodium. In the kidneys, this system can either increase sodium reabsorption or water reabsorption to alter blood volume in the body.[ref]
Think about osmosis from science class — changing the amount of water through a membrane due to how much salt is on one side of the membrane. The kidneys regulate sodium concentration to regulate fluid in this same way.
Angiotensin system and POTS:
When the renin-angiotensin-aldosterone system is involved in causing POTS, there can be an increase in plasma angiotensin II. This increase causes an imbalance in blood volume due to the kidneys not retaining enough sodium. Additionally, some researchers have found that there is inadequate ACE2 activity.[ref][ref]
Vasoconstriction and POTS:
Some people with POTS have issues with the sympathetic nervous system not working correctly in the feet and legs. When standing up, it can result in insufficient vasoconstriction (e.g., blood vessels are too relaxed). As a result, blood pools in legs and feet, as well as the abdominal cavity. The lack of vasoconstriction and the pooling blood then kicks the heart into high gear, pumping hard to make up for the lack of blood flow.[ref]
Sympathetic nervous system, NET, medications, and POTS: Hyperadrenergic
One branch of the autonomic nervous system is the sympathetic nervous system (fight-or-flight response).
The activation of the sympathetic nervous system releases norepinephrine. Norepinephrine (aka noradrenaline) functions as a neurotransmitter and a stress hormone in the body.
Adrenergic system and POTS:
A subset of people with POTS have what is known as the ‘hyperadrenergic’ form. When these people stand, their bodies release an excess of norepinephrine. It can cause heart palpitations, tremors, rapid heartbeat, feeling anxious, and increased blood pressure. Some patients with hyperadrenergic POTS also get headaches upon standing.[ref][ref]
Alternatively, instead of releasing excess norepinephrine, the body may not clear out the normal norepinephrine quickly enough. Or both could occur together.
Alterations in the norepinephrine transporter (NET) can cause reduced clearance of norepinephrine, leaving the sympathetic nervous system in a state of excessive activation. Rare mutations and more common gene variants that code for NET (norepinephrine transporter) are linked to POTS. Additionally, certain medications are NET inhibitors – some tricyclic antidepressants and certain ADHD medications.[ref]
For example, atomoxetine (Strattera) is an ADHD medication that targets the norepinephrine transporter. In a clinical trial, it has been shown to significantly increase the standing heart rate in POTS patients.[ref]
Autoimmunity causing POTS:
What could cause either the regulation of blood volume or the adrenergic (norepinephrine) system to go haywire?
Research shows that for many people, POTS can be due to an autoimmune attack on either the adrenergic system or the renin-angiotensin system.[ref][ref] Both systems are important in heart rate and blood flow.
For example, a small study in 2018 found that most patients with POTS in their study had angiotensin II type 1 receptor antibodies (IgG) as well as adrenergic activation, showing an autoimmune activation of that receptor. Interestingly, losartan, a commonly used hypertension medication that acts on the angiotensin II receptor, reduced the receptor activity down to the same levels as the control.[ref]
Another recent study (Aug. 2020) showed that patients with POTS were likely to have autoimmune activity towards the adrenergic receptors (α1 receptor, β2 receptor, cholinergic, and opioid receptor-like 1).[ref]
Is POTS Genetic?
Genetic mutations and POTS:
There is no one specific gene mutation that causes POTS. Rather, POTS is a syndrome that can have its genetic roots in various genes. Understanding where your genetic susceptibility lies may help you find your best treatment options.
For many people, an autoimmune condition (adrenergic system, angiotensin II receptor) triggers POTS.
The HLA genes code for an important part of our adaptive immune system. They help the body understand what is foreign (bacteria, viruses) and needs to be attacked. They also help the body understand which tissue is ‘self’ and should be left alone by the immune system.
Quite a few autoimmune diseases are linked to having different variants in the HLA genes. This HLA gene variation makes the human population resilient to lots of different and new pathogens, but this variation also makes individuals more susceptible to autoimmune disease.
However, one of the biggest risk factors is an HLA variant that is not included in 23andMe or AncestryDNA data. A study in 2019 identified the HLA-DQB1*0609 serotype as increasing the risk of POTS by over 8-fold![ref]
Other genetic variants increase susceptibility to POTS in different ways. The genes that have been identified so far by researchers include nitric oxide genes, norepinephrine (noradrenaline) transporters, and the beta2-adrenergic receptor – all of which impact blood volume regulation. (see the Genetic Variants section below).
Epigenetics and POTS:
Epigenetics refers to alterations in how the genetic code is turned on or off for translation. In a nutshell, the nucleus of every cell contains the complete genome, but only certain genes remain essential for that cell to function. Epigenetic markers control how often a gene is translated into its protein.
It goes hand-in-hand with the research showing that people with genetic variants that reduce the function of the SLC6A2 gene are also more susceptible to POTS. (See genetics section below).
Triggers of POTS:
Vaccines and POTS:
One trigger for POTS for some individuals seems to be certain vaccines. For example, there are dozens of case reports of POTS shortly following the HPV vaccine. Additionally, several studies followed a number of women after the HPV shot, finding an increase in dysautonomia and POTS.[ref][ref][ref][ref][ref]
Why would an HPV vaccine cause POTS in a minority of people? Some researchers point to an autoimmune response (adrenergic receptor antibodies) due to molecular mimicry with specific HPV peptides.[ref]
There are, of course, a lot of unanswered questions on the links between the HPV vaccine and POTS. Epidemiological studies often don’t find a statistical, population-wide link between the introduction of the HPV virus and the number of POTS diagnoses.[ref][ref] Additionally, some researchers point to media coverage as a cause for any post-vaccination symptom spikes.[ref]
COVID and POTS:
Interestingly, one of the mechanisms that cause POTS is a disturbance in the renin-angiotensin system, possibly due to inadequate ACE2 activity.[ref] A study of 38 people with POTS had lower ACE2 activity than the healthy control group.[ref]
Researchers discovered early on (Aug. 2020) that the SARS-CoV-2 virus may cross-react with autoimmune target proteins. The researchers caution that people who have had Covid may be at an increased risk for autoimmune conditions.[ref]
- A case series that included 20 patients explained that POTS is a common autonomic disorder following Covid.[ref]
- POTS is also common in people with long Covid.[ref]
- POTS is common enough in long Covid to have it now characterized as one of the defined subtypes.[ref]
POTS Genotype Report
Lifehacks for POTS: Diet, supplements, apps, and treatments
Related Articles and Topics:
Ehlers Danlos Syndrome Genes:
This article explores the research on Ehlers-Danlos syndrome and explains the genetic mutations that cause some of the subtypes of the disorder. You can check your genetic data (23andMe version 5 data) and learn more about how collagen disorders affect people.
Chronic headaches, sinus drainage, itchy hives, problems staying asleep, and heartburn — all of these symptoms can be caused by the body not breaking down histamine very well. Your genetic variants could be causing you to be more sensitive to foods high in histamine. Check your genetic data to see if this could be at the root of your symptoms.
Mast cells: MCAS, genetics, and solutions
Mast Cell Activation Syndrome, or MCAS, is a recently recognized disease involving mast cells that are misbehaving in various ways. Symptoms of MCAS can include abdominal pain, nausea, itching, flushing, hives, headaches, heart palpitations, anxiety, brain fog, and anaphylaxis.
HLA-B27: Genetic Variant That Increases Susceptibility to Autoimmune Diseases
Our immune system does an awesome job (most of the time) of fighting off pathogenic bacteria and viruses. But to fight off these pathogens, the body needs to know that they are the bad guys. This is where the HLA system comes in. This article covers background information on HLA-B27 and the genetic variants available in 23andMe or AncestryDNA data.
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